Publications by authors named "Yuan-Han Qin"

72 Publications

The Involvement of Neutrophil Extracellular Traps in Disease Activity Associated With IgA Vasculitis.

Front Immunol 2021 3;12:668974. Epub 2021 Sep 3.

Department of Pediatrics, The First Affiliated Hospital, Guangxi Medical University, Nanning, China.

Objectives: This aim of this study was to determine whether neutrophil extracellular traps (NETs) are involved in the pathogenesis of IgA vasculitis (IgAV) and investigate whether the circulating NETs levels are associated with disease activity in children.

Methods: We performed a case-control study and collected blood samples from 193 children with different stages of IgAV (61 were at the onset stage, 64 at the remission stage, 43 at the active stage, and 25 were undergoing drug withdrawal). A total of 192 healthy children were recruited as controls. Circulating cell free DNA (cf-DNA) was obtained from the plasma and quantified by using the Quant-iT PicoGreen DNA quantification kit. NETs-associated myeloperoxidase-DNA (MPO-DNA), citrullinated-histone H3 (cit-H3), neutrophil elastase (NE), and the deoxyribonuclease I (DNase I) concentrations were measured using enzyme-linked immunosorbent assays. The presence of NETs in the kidney and gastrointestinal tissues of onset and active IgAV patients was determined by multiple immunofluorescence staining in 15 IgAV nephritis patients and 9 IgAV patients without IgAV nephritis, respectively. NETs degradation potency of collected sera samples from IgAV patients were checked . Relationships between circulating levels of cf-DNA with MPO-DNA, NE, and DNase I and the patients were analyzed.

Results: Circulating levels of cf-DNA in onset and active IgAV patients were significantly higher than those in remission and drug withdrawal patients as well as healthy controls. The results were similar for MPO-DNA and NE. The levels of circulating cf-DNA correlated significantly with MPO-DNA, NE and DNase I. A significantly decreased degradation of NETs from the onset and active IgAV patients was observed, but was normal in healthy controls. Furthermore, presence of NETs was also confirmed in all renal and gastrointestinal tissues obtained from the onset and active IgAV patients but not control samples.

Conclusions: Our data showed that NETs were released into the circulation of IgAV patients and are involved in the disease activity. The circulating levels of NETs maybe used to assess disease severity in children with IgAV.
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http://dx.doi.org/10.3389/fimmu.2021.668974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446352PMC
October 2021

ATRA attenuate proteinuria via downregulation of TRPC6 in glomerulosclerosis rats induced by adriamycin.

Ren Fail 2018 Nov;40(1):266-272

a Department of Pediatric Nephrology , The First Affiliated Hospital of GuangXi Medical University , Nanning , China.

Objective: In this research, we explored the molecular mechanism of proteinuria in glomerulosclerosis rats and the protective effects of ATRA.

Methods: This research set up three groups: SHO group, GS group, and ATRA group (15 mg/(kg d), Sigma, St. Louis, MO). The serum creatinine (Scr), urea nitrogen (BUN), and 24-h proteinuria were detected 12 weeks after administration of ATRA. The pathological and ultrastructure changes were observed under light microscope and transmission electron microscope. The protein expression of TGF-β and Col-IV in glomerulus was detected by immunohitochemistry method. The mRNA and the protein expression of glomerular TRPC6 were detected by RT-PCR and Western blot.

Results: In the rat model of GS, the expressions of TRPC6 were significantly elevated compared with the normal rat group; however, the use of ATRA down-regulated the expression of TRPC6 in the glomeruli and attenuated glomerulosclerosis and proteinuria. Scr and BUN were also improved by the treatment of ATRA.

Conclusions: Our results demonstrated that ATRA could ameliorate glomerulosclerosis and proteinuria in GS, which may be related to suppressed expression of TRPC6.
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http://dx.doi.org/10.1080/0886022X.2018.1456459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6014515PMC
November 2018

[Research advances in the protective effect of all-trans retinoic acid against podocyte injury].

Zhongguo Dang Dai Er Ke Za Zhi 2017 Jun;19(6):719-723

Department of Pediatrics, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.

All-trans retinoic acid (ATRA) is a vitamin A derivative and plays an important role in the regulation of cell aggregation, differentiation, apoptosis, proliferation, and inflammatory response. In recent years, some progress has been made in the role of ATRA in renal diseases, especially its protective effect on podocytes. This article reviews the research advances in podocyte injury, characteristics of ATRA, podocyte differentiation and regeneration induced by ATRA, and the protective effect of ATRA against proliferation, deposition of fibers, and apoptosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7390304PMC
June 2017

Highlight the caution use of gastrointestinal prokinetic antibiotics in patient with Henoch-Schönlein purpura.

Turk J Gastroenterol 2017 03 25;28(2):142-143. Epub 2017 Jan 25.

Department of Pediatric Nephrology, The First Affiliated Hospital of GuangXi Medical University, Nanning, China; Department of Pediatric, Affiliated Hospital of Hebei University, Baoding, China.

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http://dx.doi.org/10.5152/tjg.2017.17649DOI Listing
March 2017

Neutral endopeptidase and natriuretic peptide receptors participate in the regulation of C-type natriuretic peptide expression in renal interstitial fibrosis.

J Recept Signal Transduct Res 2017 Feb 8;37(1):71-83. Epub 2016 Jun 8.

c Department of Pediatrics , First Affiliated Hospital of Guangxi Medical University , Nanning , People's Republic of China.

The initiation and progression of renal interstitial fibrosis (RIF) is a complicated process in which many factors may play an activate role. Among these factors, C-type natriuretic peptide (CNP) is an endothelium-derived hormone and acts in a local, paracrine fashion to regulate vascular smooth muscle tone and proliferation. In this study, we established a rat model of unilateral ureteral obstruction (UUO). CNP expression tends to be higher immediately after ligation and declined at later time points, occurring predominantly in tubular epithelial cells. A high-level CNP may contribute to the elevated expression of natriuretic peptide receptor (NPR)-B in the early phase of UUO. However, the sustained expression of NPR-C and neutral endopeptidase (NEP) observed throughout the study period (that is up to 3 months) helps to, at least partly, explain the subsequent decline of CNP. Thus, NEP and NPRs participate in the regulation of CNP expression in RIF.
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http://dx.doi.org/10.3109/10799893.2016.1155068DOI Listing
February 2017

Comment on a meta-analysis of re-treatment for intravenous immunoglobulin-resistant Kawasaki disease.

Cardiol Young 2016 Jun 16;26(5):1036. Epub 2016 Mar 16.

1Department of Pediatric Nephrology,The First Affiliated Hospital of GuangXi Medical University,Nanning,China.

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http://dx.doi.org/10.1017/S1047951116000172DOI Listing
June 2016

Therapeutic effect of CNP on renal osteodystrophy by antagonizing the FGF-23/MAPK pathway.

J Recept Signal Transduct Res 2016 13;36(2):213-9. Epub 2015 Oct 13.

c Department of Pediatrics , The First Affiliated Hospital of Guangxi Medical University , Nanning , People's Republic of China.

Renal osteodystrophy (ROD) is highly prevalent in chronic kidney disease (CKD). Because most patients with ROD are asymptomatic in the early stage and bone biopsy remains not a routine procedure in many clinical settings; therefore, several biochemical parameters may help to identify the existence of ROD. C-type natriuretic peptide (CNP) is considered as a positive regulator of bone formation. Both urinary excretion and renal expression of CNP are markedly up-regulated in the early stages of CKD, whereas they are still progressively declined accompanied by CKD progression, which invites speculation that the progressive decline of CNP may contribute, in part, to the pathogenesis of ROD. In addition, fibroblast growth factor (FGF)-23 is a bone-derived endocrine regulator of phosphate homeostasis. The elevation of serum FGF-23 has been recognized as a common feature in CKD to maintain normophosphatemia at the expense of declining 1,25-dihydroxyvitamin D values. Since the effects of CNP and FGF-23 on bone formation appear to oppose each other, it is reasonable to propose a direct interaction of their signaling pathways during the progression of ROD. CNP and FGF-23 act through a close or reciprocal pathway and are in agreement with recent studies demonstrating a down-regulatory role of the mitogen-activated protein kinase activity by CNP. The specific node may act at the level of RAF-1 through the activation of cyclic guanosine monophosphate-dependent protein kinases II.
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http://dx.doi.org/10.3109/10799893.2015.1075041DOI Listing
November 2016

Exogenous C-type natriuretic peptide infusion ameliorates unilateral ureteral obstruction-induced tubulointerstitial fibrosis in rats.

Lab Invest 2015 Mar 1;95(3):263-72. Epub 2014 Dec 1.

Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning, People's Republic of China.

Although many experimental therapeutic roles for C-type natriuretic peptide (CNP) have been documented in the field of cardiovascular and pulmonary-vascular disease, the therapeutic uses of CNP to nephropathies are not as well documented. In this study, we established a rat model of unilateral ureteral obstruction (UUO) to observe the beneficial effects of CNP on tubulointerstitial fibrosis (TIF). In UUO rats, CNP administration induced a significant increase in plasma CNP levels, and caused a significant decrease in blood urea nitrogen and creatinine levels. In addition, CNP infusion also alleviated the pathological lesions and collagen IV accumulation in the obstructed kidneys through downregulation of tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 expression. In conclusion, exogenous CNP infusion can ameliorate UUO-induced TIF in rats. However, the use of CNP as a therapeutic agent requires further evaluation before being considered for human TIF.
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http://dx.doi.org/10.1038/labinvest.2014.149DOI Listing
March 2015

The potential signaling pathway between peroxisome proliferator-activated receptor gamma and retinoic acid receptor alpha in renal interstitial fibrosis disease.

J Recept Signal Transduct Res 2015 31;35(4):258-68. Epub 2014 Oct 31.

b Department of Nephrology , The Six Affiliated Hospital of Sun Yat-Sen University , Guangzhou , China.

Peroxisome proliferator-activated receptorγ (PPARγ) can regulate the process of cell apoptosis and is related to the progression of renal disorders. Retinoic acid receptor alpha (RARα) is one of the nuclear receptors involved in a variety of kidney diseases. Renal interstitial fibrosis (RIF) is a common denominator of chronic kidney disease (CKD). This study investigated whether a potential signaling pathway existed between PPARγ and RARα in RIF rats with unilateral ureteral obstruction (UUO). The rats were randomly divided into four groups: a model group subjected to UUO (GU), and three other groups treated with rosiglitazone sodium (GRS), GW9662 and dimethyl sulfoxide (DMSO), n = 40, respectively. Renal tissues were collected two and four weeks after post-surgery. The relevant indicators were detected. In comparison with the GU group, the expressions of PPARγ and RARα (protein and mRNA) were increased in the GRS group, and decreased in the GW9662 group (all p < 0.01). The RIF index, mRNA and protein expression of transforming growth factor-β1 (TGF-β1), and the protein expressions of collagen-IV (Col-IV) and fibronectin (FN) in the GRS group were more markedly reduced than those in the GU group; their levels in the GW9662 group were elevated (all p < 0.01). PPARγ or RARα was negatively correlated to the RIF index, TGF-β1, Col-IV and FN. PPARγ was positively correlated with RARα (all p < 0.01). In conclusion, PPARγ agonist can elevate the expression of PPARγ or RARα in RIF rats. There might be a potential signaling pathway between PPARγ and RARα in RIF disease.
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http://dx.doi.org/10.3109/10799893.2014.975249DOI Listing
August 2016

GSTT1 polymorphism and the risk of developing prostate cancer.

Am J Epidemiol 2014 Jul 6;180(1):1-10. Epub 2014 Jun 6.

A possible association between glutathione S-transferase theta 1 gene (GSTT1) polymorphism and the risk of developing prostate cancer is currently hotly debated, but evidence from various epidemiologic studies remains unclear. This investigation was performed to assess whether an association between GSTT1 polymorphism and prostate cancer risk exists by using meta-analysis to combine comparable studies, thereby increasing sample size and statistical significance, as well as to identify patterns in various studies. The association reports were identified from the PubMed database and the Cochrane Library on March 1, 2013, and data from eligible studies (from 1999-2012) were synthesized. Thirty-eight reports were included in this meta-analysis on the association of the null genotype of GSTT1 with prostate cancer risk. No solid association between the GSTT1 null genotype and prostate cancer risk could be established for the overall population (odds ratio = 1.11, 95% confidence interval: 0.97, 1.27; P = 0.13). However, the GSTT1 null genotype was distinctly associated with prostate cancer risk in Caucasians (odds ratio = 1.24, 95% confidence interval: 1.03, 1.48, P = 0.02). In conclusion, the GSTT1 null genotype is associated with prostate cancer risk in Caucasians, but not in the overall population.
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http://dx.doi.org/10.1093/aje/kwu112DOI Listing
July 2014

The role of retinoic acid receptors in the signal pathway of all-trans retinoic acid-induced differentiation in adriamycin-induced podocyte injury.

J Recept Signal Transduct Res 2014 Dec 20;34(6):484-92. Epub 2014 May 20.

Department of Pediatrics, The First Affiliated Hospital of GuangXi Medical University , Nanning , China .

All-trans retinoic acid (ATRA) plays an essential role in cell survival and differentiation by binding to retinoic acid receptors (RARs), including RAR-α, RAR-β, and RAR-γ. Injury to podocytes is the most frequent cause of glomerulosclerosis (GS). This study was performed to investigate which of the RAR subtypes is involved in the signal pathway of ATRA-induced differentiation of injured podocytes. ATRA (0.1 μM) was administered to Adriamycin (ADR)-induced, injured podocytes, in vitro. Morphological changes were observed. The protein/mRNA expression of podocin, nephrin, transforming growth factor β1(TGF-β1), and the RARs (RAR-α,β,γ) was measured by RT-PCR and Western blotting. ATRA treatment ameliorated cell hypertrophy and reduced the shedding of the cytoplasm which was observed under light microscope and the extension of the foot processes was observed under scan electron microscope. Compared with the injured podocytes, ATRA exposure significantly increased the protein/mRNA expression of nephrin and podocin and it markedly reduced TGF-β1 (all p < 0.05). Compared with the injured podocytes, the protein/mRNA expression of RAR-α and RAR-γ was significantly increased after ATRA exposure; however, the expression level of RAR-β was not significantly different. The RAR-α/γ protein expression level was positively correlated with nephrin and podocin (-α, r = 0.637, 0.663; -γ, r = 0.882, 0.878; all p < 0.05), and negatively correlated with TGF-β1 (-α, r = -0.650; -γ, r = -0.739; all p < 0.05). The RAR-β protein expression level was not correlated with nephrin, podocin and TGF-β1 (r = -0.312, 0.079, -0.279; all p > 0.05). In conclusion, RAR-α/γ (and RAR-β to a lesser degree) may be involved in the signal pathway of ATRA-induced differentiation in injured podocytes.
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http://dx.doi.org/10.3109/10799893.2014.920394DOI Listing
December 2014

Distribution of pathological finding in the children with nephrotic syndrome from Guangxi.

Saudi J Kidney Dis Transpl 2014 May;25(3):684-8

Department of Pediatric Nephrology, The First Affiliated Hospital of GuangXi Medical University, Nanning, China.

To identify the variations in pediatric renal biopsy pathology and clinicopathological features in Guangxi, China, in the past ten years, we studied retrospectively the kidney biopsies performed to evaluate the primary nephrotic syndrome (PNS) in 218 children at two main medical centers in Guangxi from January 1999 to January 2009. The major pathological finding was mesangial proliferative glomerulonephritis (48.2%), focal segmental glomerulosclerosis (16.5%), immunoglobulin A nephropathy (13.3%) and minimal change disease (11.0%). Patients with different pathological types yielded different response rates to glucocorticoids (P <0.001). There were statistical significant differences between prognosis for the different pathological types (P <0.05). The pathological characteristics of PNS in children were diverse and significant for guiding the grade of glucocorticoid response and predicting the prognosis of the PNS disease.
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http://dx.doi.org/10.4103/1319-2442.132240DOI Listing
May 2014

LIM homeobox transcription factor 1B expression affects renal interstitial fibrosis and apoptosis in unilateral ureteral obstructed rats.

Am J Physiol Renal Physiol 2014 Jun 30;306(12):F1477-88. Epub 2014 Apr 30.

Cellular Stress and Ageing Program, Bionanoscience and Bio-Imaging Program, Bio&Nano-Solutions, Düsseldorf, Germany.

LIM homeobox transcription factor 1B (LMX1B) is a transcription factor of the LIM homeodomain type and has been implicated in the development of diverse structures such as limbs, kidneys, eyes, and the brain. Furthermore, LMX1B has been implicated in nail-patella syndrome, which is predominantly characterized by malformation of limbs and nails, and in 30% of patients, nephropathy, including renal fibrosis, is observed. Since no reports were available that studied the link between LMX1B expression and renal interstitial fibrosis, we explored if LMX1B affects typical markers of fibrosis, e.g., extracellular matrix components, profibrotic factors, and apoptosis as the final detrimental consequence. We recently showed that LMX1B acts as a negative regulator of transforming growth factor-βl, collagen type III, fibronectin, cleaved caspase-3, and the cell apoptosis rate in a renal tubular epithelial cell system under hypoxic conditions. Here, we confirmed these results in unilateral ureteral obstructed rats. Furthermore, LMX1B was distinctly expressed throughout the glomerulus and tubule lining, including epithelial cells. Knockdown of LMX1B aggravated the expression of fibrosis markers, oxidative stress, and apoptosis compared with the already increased levels due to unilateral ureteral obstruction, whereas overexpression attenuated these effects. In conclusion, reduced LMX1B levels clearly represent a risk factor for renal fibrosis, whereas overexpression affords some level of protection. In general, LMX1B may be considered to be a negative regulator of the fibrosis index, transforming growth factor-βl, collagen type III, fibronectin, cleaved caspase-3, cell apoptosis, ROS, and malondialdehyde (r = -0.756, -0.698, -0.921, -0.923, -0.843, -0.794, -0.883, and -0.825, all P < 0.01).
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http://dx.doi.org/10.1152/ajprenal.00600.2013DOI Listing
June 2014

Retracted Association of STAT4 gene polymorphism with systemic lupus erythematosus / lupus nephritis risk.

Nephrology (Carlton) 2014 Apr 16. Epub 2014 Apr 16.

Department of Nephrology, the Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510655, China.

Objective: The association of STAT4 gene polymorphism with systemic lupus erythematosus (SLE) / lupus nephritis (LN) results from the published studies is still conflicting. This meta-analysis was performed to evaluate the relationship between STAT4 rs7574865, rs16833431, rs11889341, rs8179673, rs10168266, rs7582694, rs3821236, rs7601754 gene polymorphism and SLE / LN, and to explore whether STAT4 gene polymorphism could become a predictive marker for SLE / LN risk.

Methods: Association studies were identified from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database) as of September 1, 2013, and eligible investigations were synthesized using meta-analysis method.

Results: 24 investigations were identified for the analysis of association between STAT4 gene polymorphism and SLE, consisting of 31190 patients with SLE and 43940 controls. In STAT4 rs7574865, there was a marked association between T allele or TT genotype and SLE susceptibility (T: OR=1.53, 95% CI: 1.30-1.79, P<0.00001; TT: OR=1.60, 95% CI: 1.34-1.92, P<0.00001), and GG homozygous was associated with SLE risk (OR=0.62, 95% CI: 0.51-0.75, P<0.00001). Furthermore, rs8179673, rs7582694, or rs3821236 minor allele frequency was associated with the risk of SLE, but this association was not found in rs16833431, rs11889341, rs10168266, rs7601754, however, the number of included studies was small and the results were less robust. In addition, STAT4 rs7574865 gene polymorphism was not associated with the LN risk.

Conclusions: Our results indicate that T allele or TT homozygous is a significant risk genetic molecular marker to predict the SLE susceptibility and GG genotype is a valuable marker to against the SLE risk, but the association was not found for LN. However, more investigations are required to further clarify the association of the T allele or TT homozygous with SLE / LN susceptibility.
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http://dx.doi.org/10.1111/nep.12264DOI Listing
April 2014

Potential signal pathway of all-trans retinoic acid for MMP-2 and MMP-9 expression in injury podocyte induced by adriamycin.

J Recept Signal Transduct Res 2014 Oct 2;34(5):378-85. Epub 2014 Apr 2.

Department of Pediatrics, The First Affiliated Hospital of GuangXi Medical University , NanNing , China and.

All-trans-retinoic acid (ATRA) can regulate some specific genes expression in various tissue and cells via nuclear retinoic acid receptors (RARs), including three subtypes: retinoic acid receptor-alpha (RAR-α), retinoic acid receptor-beta (RAR-β) and retinoic acid receptor-gamma (RAR-γ). Podocyte injury plays a pivotal role in the progression of glomerulosclerosis (GS). This study was performed to study the potential signal pathway of ATRA in the expression of matrix metalloproteinases-2 (MMP-2) and matrix metalloproteinases-9 (MMP-9) in injury podocyte. Cells were divided into three groups: group of negative control (NC), group of injury podocyte induced by adriamycin (ADR) (AI) and group of ADR inducing podocyte injury model treated with ATRA (AA). The cells morphology changes were detected using microscope and scanning electron microscopy. MMP-2 and MMP-9 enzymic activity was detected using the gelatin zymography method. Protein and mRNA expressions of MMP-2, MMP-9, RAR-α, RAR-β and RAR-γ were measured by western-blot and real-time RT-PCR. Enzymatic activity of MMP-2 and MMP-9 in group AA was significantly enhanced compared to AI group after ATRA-treated 24 h (p < 0.05). The protein and mRNA expressions of MMP-2/MMP-9 in group AA were significantly increased than those in group AI at both 12 and 24 h time points (p < 0.05). Compared to group AI, RAR-α and RAR-γ protein/mRNA expressions of group AA were significantly increased at both 12 and 24 h time points (p < 0.05). There was no difference for the expression of RAR-β between group AI and group AA (p > 0.05). RAR-α protein level was positively correlated with MMP-2 or MMP-9 protein expression (p < 0.05), and RAR-γ protein level was also positively correlated with MMP-2 or MMP-9 protein expression (p < 0.05). In conclusion, ATRA may increase expression of MMP-2 and MMP-9 by the potential signal pathway of RAR-α and RAR-γ in injury podocyte induced by adriamycin, but not RAR-β.
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http://dx.doi.org/10.3109/10799893.2014.904873DOI Listing
October 2014

Association of prohibitin-1 and 2 with oxidative stress in rats with renal interstitial fibrosis.

Mol Biol Rep 2014 May 5;41(5):3033-43. Epub 2014 Mar 5.

Department of Nephrology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510655, China,

Prohibitins PHB1 and PHB2 are evolutionary conserved and pleiotropic proteins, which have been shown to be important factors in various cellular functions, including proliferation, tumour suppression, apoptosis, transcription, and mitochondrial protein folding. Recently, we demonstrated that down-regulation promoted renal interstitial fibrosis (RIF) in ureteral obstructed rats. Furthermore, the hypoxic conditions and oxidative stress have been implicated in obstruction-mediated renal disease. This study was performed to explore the association of PHBs with oxidative stress in a rat model of RIF. PHBs, the pro-fibrotic transforming growth factor-β1 (TGF-β1), and the extracellular matrix proteins collagen-IV (Col-IV) and fibronectin (FN) were evaluated, as were markers of oxidative stress [total reactive oxygen species (ROS), malondialdehyde (MDA)] and antioxidative capacity (superoxide dismutase, glutathione), and apoptosis. Our results showed a progressive increase in oxidative stress and concomitant decrease in antioxidants over a period of 4 weeks ureteral obstruction. Concomitantly, profibrotic components increased and PHB expression decreased. Overall, both PHBs were negatively correlated with the extent of observed fibrosis, TGF-β1, Col-IV, FN, ROS, MDA, and apoptosis.
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http://dx.doi.org/10.1007/s11033-014-3162-1DOI Listing
May 2014

Association of transforming growth factor-β1 T869C gene polymorphism with diabetic nephropathy risk.

Nephrology (Carlton) 2014 Feb;19(2):107-15

Department of Nephrology, the Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

Aim: A possible association between the transforming growth factor-β1 (TGF-β1) T869C gene polymorphism and the risk of developing diabetic nephropathy (DN) remains unclear. This investigation was performed to assess if an association between the TGF-β1 T869C gene polymorphism and DN risk exists by using meta-analysis to combine comparable studies, thereby increasing sample size and statistical significance, and to identify patterns in various studies.

Methods: The association reports were identified from PubMed, Cochrane Library, and CBM-disc (China Biological Medicine Database) on 1 May 2013, and eligible studies were recruited and synthesized.

Results: Fifty reports were recruited into this meta-analysis for the association of the TGF-β1 T869C gene polymorphism with DN risk. The TT genotype in the overall population was shown to be associated with DN risk (odds ratio (OR) = 0.74, 95% confidence interval (CI): 0.56-0.98, P = 0.04). In the sub-group analysis, CC genotype was associated with DN risk in Asians, Caucasians, and Africans. However, the sample size for Caucasians and Africans was relatively small. Furthermore, T allele was distinctly associated with the risk of developing DN in the Asian population (OR = 0.76, 95% CI: 0.62-0.92, P = 0.005).

Conclusions: The TT genotype of TGF-β1 T869C in the overall population was associated with DN risk, whereas the CC genotype and T allele were distinctly associated with DN risk in the Asian population. Nonetheless, additional studies are required to firmly establish a correlation between the aforementioned polymorphism and DN risk.
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http://dx.doi.org/10.1111/nep.12176DOI Listing
February 2014

LIM homeobox transcription factor 1B is associated with pro-fibrotic components and apoptosis in hypoxia/reoxygenation renal tubular epithelial cells.

Apoptosis 2014 Apr;19(4):594-602

Department of Nephrology, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510655, China,

LIM homeobox transcription factor 1B (LMX1B) is a transcription factor of the LIM-homeodomain type, which plays an important role in foetal development during formation of the extremities, kidneys, eyes, and the brain. Furthermore, LMX1B has been implicated in nail-patella syndrome, which is predominantly characterized by malformation of limbs and nails, and in 30 % of patients, nephropathy, including renal fibrosis, is observed. Since no reports were available that studied the link between LMX1B expression and pro-fibrotic components and apoptosis in hypoxic renal tubular epithelial cells (RTEC), we explored if LMX1B was associated with extracellular matrix components, profibrotic factors, and apoptosis induced by hypoxia/reoxygenation (H-R). In this cell system under hypoxic conditions, when the expression of LMX1B was inhibited in H-R RTEC, the expression of transforming growth factor-βl, collagen-III, fibronectin, cleaved caspase-3, and cell apoptosis rate was increased. Consequently, overexpression of LMX1B was associated with reduced cell apoptosis, whilst downregulation of LMX1B was associated with increased cell apoptosis in H-R RTEC.
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http://dx.doi.org/10.1007/s10495-013-0952-1DOI Listing
April 2014

Prohibitin attenuates oxidative stress and extracellular matrix accumulation in renal interstitial fibrosis disease.

PLoS One 2013 25;8(10):e77187. Epub 2013 Oct 25.

Department of Pediatric Nephrology, the First Affiliated Hospital of GuangXi Medical University, NanNing, China ; Department of Nephrology, the Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

Prohibitin is an evolutionary conserved and pleiotropic protein that has been implicated in various cellular functions, including proliferation, tumour suppression, apoptosis, transcription, and mitochondrial protein folding. Both prohibitin over- and under-expression have been implicated in various diseases and cell types. We recently demonstrated that prohibitin down-regulation results in increased renal interstitial fibrosis (RIF). Here we investigated the role of oxidative stress and prohibitin expression in RIF in unilateral ureteral obstructed rats. Lentivirus-based delivery vectors were used to knockdown or over-express prohibitin. Our results show that increased prohibitin expression was negatively correlated with the RIF index, reactive oxygen species, malon dialdehyde, transforming growth factor β1, collagen IV, fibronectin, and cell apoptosis index. In conclusion, we postulate that prohibitin acts as a positive regulator of mechanisms that counteract oxidative stress and extracellular matrix accumulation and therefore has an antioxidative effect.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0077187PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3808389PMC
August 2014

Paradoxical expressions of natriuretic peptide receptor-C and neutral endopeptidase account for C-type natriuretic peptide decline during the progression of experimental obstructive nephropathy.

J Renin Angiotensin Aldosterone Syst 2014 Dec 4;15(4):458-65. Epub 2013 Nov 4.

Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, China.

Introduction: C-type natriuretic peptide (CNP) selectively binds to the guanylyl cyclase coupled natriuretic peptide receptor (NPR)-B and exerts more potent antihypertrophic and antifibrotic properties. Elimination of CNP occurs mainly by neutral endopeptidase (NEP) and NPR-C.

Methods: We established a rat model of unilateral ureteral obstruction (UUO) to examine the continuous change of the CNP expression and to assess the correlations of NPR-B, NPR-C, NEP with CNP in the obstructed kidneys.

Results: The expressions of CNP mRNA and protein in the obstructed kidneys tended to be higher immediately after ligation and declined at later time points compared to sham-operated rats, measured by real-time polymerase chain reaction (PCR) and western blot analysis. Subsequent correlation analysis indicated that CNP mRNA was positively correlated with NPR-B mRNA (r=+0.673, p<0.05). In addition, the increased expression of NPR-C (r=-0.943 and -0.837 for mRNA and protein respectively, p<0.05) and NEP (r=-0.687 and -0.823 for mRNA and protein respectively, p<0.05) were accompanied by a significant decline in CNP.

Conclusions: A high level of CNP may contribute to the elevated expression of NPR-B in the early phase of UUO. More interestingly, paradoxical expressions of NPR-C and NEP may account for the decline of CNP in the obstructed kidneys.
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http://dx.doi.org/10.1177/1470320313507121DOI Listing
December 2014

Prohibitin is associated with antioxidative protection in hypoxia/reoxygenation-induced renal tubular epithelial cell injury.

Sci Rep 2013 Nov 4;3:3123. Epub 2013 Nov 4.

1] Department of Pediatric Nephrology, the First Affiliated Hospital of GuangXi Medical University, NanNing 530021, China [2] Department of Nephrology, the Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China [3].

Prohibitin is an evolutionary conserved and pleiotropic protein that has been implicated in various cellular functions, including proliferation, tumour suppression, apoptosis, transcription, and mitochondrial protein folding. We recently demonstrated that prohibitin downregulation results in increased renal interstitial fibrosis. Here we investigated the role of oxidative stress and prohibitin expression in a hypoxia/reoxygenation injury system in renal tubular epithelial cells with lentivirus-based delivery vectors to knockdown or overexpress prohibitin. Our results show that increased prohibitin expression was negatively correlated with reactive oxygen species, malon dialdehyde, transforming-growth-factor-β1, collagen-IV, fibronectin, and apoptosis (r = -0.895, -0.764, -0.798, -0.826, -0.817, -0.735; each P < 0.01), but positively correlated with superoxide dismutase, glutathione and mitochondrial membrane potential (r = 0.807, 0.815, 0.739; each P < 0.01). We postulate that prohibitin acts as a positive regulator of mechanisms that counteract oxidative stress and extracellular matrix accumulation and therefore has an antioxidative effect.
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http://dx.doi.org/10.1038/srep03123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3816288PMC
November 2013

Association of peroxisome proliferator-activated receptors/retinoic acid receptors with renal diseases.

J Recept Signal Transduct Res 2013 Dec 19;33(6):349-52. Epub 2013 Sep 19.

Department of Nephrology, The Sixth Affiliated Hospital of Sun Yat-Sen University , Guangzhou , China .

Peroxisome proliferator-activated receptor-γ (PPARγ), belongs to the nuclear receptor superfamily, and is a nuclear transcription receptor involving in the regulation of several biochemical pathways, such as cell growth, differentiation, and apoptosis. The nuclear retinoic acid receptors (RARs) are transcriptional transregulators that control the expression of specific subsets of genes in a ligand-dependent manner, and include three subtypes (RARα, RARβ, and RARγ). These control the expression of specific gene subsets subsequent to ligand binding and to strictly control phosphorylation processes. The current status of knowledge indicates that there might be inter- or overlapping actions between PPARγ and RARs, and there might be an association of PPARγ/RARs with renal diseases. Various agonists of both receptor families seem to prevent or retard the progression of renal disease. Herein, we review if causal relationships can be established between PPARγ/RARs and renal diseases and its manifestations.
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http://dx.doi.org/10.3109/10799893.2013.838786DOI Listing
December 2013

Prohibitin 1 expression is associated with prohibitin 2 expression in renal interstitial fibrosis rats.

Ren Fail 2013 2;35(10):1465. Epub 2013 Sep 2.

Department of Pediatric Nephrology, The First Affiliated Hospital of Guangxi Medical University , Guangxi, NanNing , China ;

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http://dx.doi.org/10.3109/0886022X.2013.829404DOI Listing
June 2014

Simplified stereological evaluation of renal morphology after unilateral ureteral obstruction.

Int J Med Sci 2013 21;10(4):385-91. Epub 2013 Feb 21.

Department of Pediatrics, the First Affiliated Hospital of Anhui Medical University, No. 218 Ji-Xi Road, Hefei 230022, PR China.

Objective And Methods: This study established a simple stereological method to obtain quantitative information about two- or three-dimensional structures based on observations from kidney sections in the unilateral ureteral obstruction(UUO) model.

Results: Tubulointerstitial area(TA) and TA/the area of a rectangular field(RA) were raised gradually, but significantly, in the obstructed kidney from 1 to 3months post-ligation in comparison to the sham kidney of sham-operated rats(SOR). On the contrary, glomerular area(GA) and glomerular volume(GV) were decreased progressively over time, but significantly, in the obstructed kidney from 3weeks to 3months post-ligation compared to the sham kidney of SOR. UUO caused a progressive decline of TA and TA/RA in the contralateral kidney. More specifically, there were significant decreases in TA at 1,2,3months post-ligation, while in TA/RA only at 3months post-ligation in comparison to the right kidney of SOR. In contrast, GA and GV enhanced in a time-dependent manner in the contralateral kidney, in which the difference in GA reached significance only at 3months post-ligation, whereas the difference in GV reached significance from 1 to 3months post-ligation when comparing with the right kidney of SOR.

Conclusions: Our results confirmed two typical features of obstructive nephropathy, including widen interstitial space and glomerular atrophy in the obstructed kidney, and compensatory growth of the contralateral kidney.
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http://dx.doi.org/10.7150/ijms.5182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3590597PMC
September 2013

The controversial role of retinoic acid in fibrotic diseases: analysis of involved signaling pathways.

Int J Mol Sci 2012 Dec 21;14(1):226-43. Epub 2012 Dec 21.

Department of Pediatric Nephrology, the First Affiliated Hospital of Guangxi Medical University, 1 Nanning 53002, China.

Fibrotic diseases, such as liver, pulmonary and renal fibrosis, are common end-stage conditions and represent a major global health problem. Furthermore, effective therapeutic measures are presently unavailable. Extracellular matrix accumulation is the most prominent characteristic in the pathogenesis of fibrotic disease. Retinoic acid, including all-trans retinoic acid, 9-cis and 13-cis retinoic acid, play important roles in various physiological processes, such as in embryonic development, reproduction, vision, cell growth, differentiation, apoptosis and inflammation. Present studies report that retinoic acid treatment may affect various processes involved in the onset and progression of fibrotic disease. However, the therapeutic effects of retinoic acid in such diseases remain controversial. Several reports indicate that retinoic acid positively affects the progression of fibrosis and alleviates the accumulation of the extracellular matrix, whereas other studies report the opposite; that retinoic acid exacerbates fibrosis and induces extracellular matrix accumulation. Signaling pathways might be an important influencing factor and differences in signaling events might be responsible for the contradictory role of retinoic acid in fibrotic diseases. Since there was no review available that investigated the role of retinoic acid and the signaling pathways involved, we retrospectively studied the literature and provide a comprehensive analysis of retinoic acid's role in fibrotic diseases, and provide an overview of the signal transduction pathways involved in its pathogenesis.
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http://dx.doi.org/10.3390/ijms14010226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3565260PMC
December 2012

Signaling pathways of prohibitin and its role in diseases.

J Recept Signal Transduct Res 2013 18;33(1):28-36. Epub 2013 Jan 18.

Department of Pediatric Nephrology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.

Prohibitin (PHB), appearing to be a negative regulator of cell proliferation and to be a tumor suppressor, has been connected to diverse cellular functions including cell cycle control, senescence, apoptosis and the regulation of mitochondrial activities. It is a growth regulatory gene that has pleiotropic functions in the nucleus, mitochondria and cytoplasmic compartments. However, in different tissues/cells, the expression of PHB was different, such as that it was increased in most of the cancers, but its expression was reduced in kidney diseases. Signaling pathways might be very important in the pathogenesis of diseases. This review was performed to provide a relatively complete signaling pathways flowchart for PHB to the investigators who were interested in the roles of PHB in the pathogenesis of diseases. Here, we review the signal transduction pathways of PHB and its role in the pathogenesis of diseases.
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http://dx.doi.org/10.3109/10799893.2012.752006DOI Listing
July 2013

Anti-neutral endopeptidase, natriuretic peptides disarrangement, and proteinuria onset in membranous nephropathy.

Mol Biol Rep 2013 Apr 28;40(4):2963-7. Epub 2012 Dec 28.

Department of Pediatrics, The First Affiliated Hospital of Anhui Medical University, No. 218 Ji-Xi Road, Hefei 230022, People's Republic of China.

Neutral endopeptidase (NEP) is the first podocytic antigen responsible for human membranous nephropathy (MN). Besides the prevailing pathogenetic mechanism of immune complex, NEP is also involved in the metabolism of natriuretic peptides (NP). The identification of anti-NEP antibodies in human MN suggests that the decreased circulating NEP may down-regulate the NP catabolism. In this context, we hypothesize that NP disarrangement secondary to anti-NEP antibodies may account, in part, for the onset of proteinuria in MN. Whereas the pathways for the onset of proteinuria caused by elevated NP level are still obscure. The data presented in this review focus on those which support this hypothesis with regards to evidence from the glomerular haemodynamic changes, endothelial permeability, glomerular basement membrane disruption, and podocyte detachment.
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http://dx.doi.org/10.1007/s11033-012-2367-4DOI Listing
April 2013

Zhou, T.B., et Al., correction: all-trans retinoic Acid treatment is associated with prohibitin expression in renal interstitial fibrosis rats. Int. J. Mol. Sci. 2012, 13, 2769-2782.

Int J Mol Sci 2012 Dec 18;13(12):17295. Epub 2012 Dec 18.

Department of Pediatrics, The First Affiliated Hospital of GuangXi Medical University, Nanning 530021, China.

The authors wish to change Figure 2 of the paper published in IJMS [1]. The positions of H(1) and H(2) in the previous article were reversed. These errors have been amended in an amended version of the manuscript, which is available from the International Journal of Molecular Sciences website. The authors and publisher apologize for the inconvenience. [...].
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http://dx.doi.org/10.3390/ijms131217295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3546753PMC
December 2012

Association of retinoic acid receptors with extracellular matrix accumulation in rats with renal interstitial fibrosis disease.

Int J Mol Sci 2012 Oct 31;13(11):14073-85. Epub 2012 Oct 31.

Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.

The nuclear retinoic acid receptors (RARs) function as ligand-dependent transcriptional regulators and include three subtypes (RARα, RARβ and RARγ), which control the expression of specific gene subsets subsequent to ligand binding and to strictly controlled phosphorylation processes. Extracellular matrix (ECM) accumulation is the most important characteristic of renal interstitial fibrosis (RIF). This study was performed to investigate whether RARs were associated with ECM accumulation in the progression of RIF in rats. Eighty Wistar male rats were divided into a sham operation group (SHO) and a model group subjected to unilateral ureteral obstruction (GU) at random; n = 40, respectively. The RIF disease in GU group was established by left ureteral ligation. The renal tissues were collected at two weeks and four weeks after surgery. Protein expressions of RARα, RARβ, RARγ, transforming growth factor-βl (TGF-β1), collagen-IV (Col-IV) and fibronectin (FN) were detected using immunohistochemical analysis, and mRNA expressions of RARα, RARβ, RARγ and TGF-β1 in renal tissue were detected by real time reverse transcription polymerase chain reaction. RIF index in renal interstitium was also calculated. When compared with those in SHO group, expressions of RARα and RARβ (protein and mRNA) were markedly reduced in the GU group (each p < 0.01). There was no marked difference for the expression of RARγ (protein and mRNA) between the SHO group and the GU group. The expressions of TGF-β1, Col-IV, FN and the RIF index in the GU group were markedly increased when compared with those in the SHO group (each p < 0.01). The protein expression of RARα/RARβ was negatively correlated with protein expression of TGF-β1, Col-IV or FN and the RIF index (all p < 0.01). In conclusion, the low expression of RARα/RARβ is associated with ECM accumulation in the progression of RIF in rats, suggesting that RARα/RARβ is a potentially therapeutic target for prevention of RIF.
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http://dx.doi.org/10.3390/ijms131114073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3509566PMC
October 2012

All-trans retinoic acid attenuates the renal interstitial fibrosis lesion in rats but not by transforming growth factor-β1/Smad3 signaling pathway.

Ren Fail 2013 26;35(2):262-7. Epub 2012 Nov 26.

Department of Pediatrics, The First Affiliated Hospital of GuangXi Medical University, NanNing 530021, China.

All-trans retinoic acid (ATRA) is an important therapeutic agent for prevention of the renal diseases. Transforming growth factor-β1 (TGF-β1)/Smad3 signaling pathway is a key signaling pathway which takes part in the progression of renal interstitial fibrosis (RIF). This investigation was performed to study the effect of ATRA in RIF rats and its effect on the TGF-β1/Smad3 signaling pathway. Sixty Wistar male rats were divided into three groups at random: sham operation group (SHO), model group subjected to unilateral ureteral obstruction (GU), model group treated with ATRA (GA), n = 20, respectively. RIF index, protein expression of TGF-β1, collagen-IV (Col-IV) and fibronectin (FN) in renal interstitium, and mRNA and protein expressions of Smad3 in renal tissue were detected at 14-day and 28-day after surgery. The RIF index was markedly elevated in group GU than in SHO group (p < 0.01), and the RIF index of GA group was alleviated when compared with that in GU group (p < 0.01). Compared with in group SHO, the mRNA/protein expression of Smad3 in renal tissue was significantly increased in group GU (p < 0.01). However, the mRNA and protein expressions of Smad3 in renal tissue in GA group were not markedly alleviated by ATRA treatment when compared with those in GU (each p > 0.05). Protein expressions of TGF-β1, Col-IV, and FN in GU group were markedly increased than those in SHO group (each p < 0.01), and their expressions in GA group were markedly down-regulated by ATRA treatment than those of GU group (all p < 0.01). The protein expression of Smad3 was positively correlated with RIF index, protein expression of TGF-β1, Col-IV or FN (each p < 0.01). In conclusion, ATRA treatment can alleviate the RIF progression in UUO rats. However, ATRA cannot affect the signaling pathway of TGF-β1/Smad3 in the progression of RIF.
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http://dx.doi.org/10.3109/0886022X.2012.745120DOI Listing
August 2013
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