Publications by authors named "Sophie Moog"

13 Publications

  • Page 1 of 1

Loss of SDHB Promotes Dysregulated Iron Homeostasis, Oxidative Stress, and Sensitivity to Ascorbate.

Cancer Res 2021 Jul 14;81(13):3480-3494. Epub 2021 Jun 14.

PARCC, INSERM UMR970, Equipe Labellisée par la Ligue Contre le Cancer, Paris, France.

Succinate dehydrogenase is a key enzyme in the tricarboxylic acid cycle and the electron transport chain. All four subunits of succinate dehydrogenase are tumor suppressor genes predisposing to paraganglioma, but only mutations in the SDHB subunit are associated with increased risk of metastasis. Here we generated an knockout chromaffin cell line and compared it with deficient cells. Both cell types exhibited similar SDH loss of function, metabolic adaptation, and succinate accumulation. In contrast, cells showed hallmarks of mesenchymal transition associated with increased DNA hypermethylation and a stronger pseudo-hypoxic phenotype compared with cells. Loss of SDHB specifically led to increased oxidative stress associated with dysregulated iron and copper homeostasis in the absence of NRF2 activation. High-dose ascorbate exacerbated the increase in mitochondrial reactive oxygen species, leading to cell death in cells. These data establish a mechanism linking oxidative stress to iron homeostasis that specifically occurs in -deficient cells and may promote metastasis. They also highlight high-dose ascorbate as a promising therapeutic strategy for SDHB-related cancers. SIGNIFICANCE: Loss of different succinate dehydrogenase subunits can lead to different cell and tumor phenotypes, linking stronger 2-OG-dependent dioxygenases inhibition, iron overload, and ROS accumulation following SDHB mutation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/0008-5472.CAN-20-2936DOI Listing
July 2021

Recurrence-free survival analysis in locally advanced pheochromocytoma: first appraisal.

J Clin Endocrinol Metab 2021 Mar 30. Epub 2021 Mar 30.

Endocrine oncology unit, Gustave Roussy, F-94805, Villejuif, France.

Context: Locally advanced pheochromocytoma (LAP) behavior remains unknown.

Objective: To characterize this population and its recurrence-free survival (RFS).

Design: A retrospective multicentric study run within the ENDOCAN-COMETE network and GTE from 2003 to 2018.

Setting: 11 French Referral centers.

Patients: Patients with LAP as defined by capsular invasion, vascular invasion, adipose tissue invasion and/or positive locoregional lymph nodes at diagnosis without evidence of distant metastasis.

Main Outcome Measures: Recurrence was defined as the reappearance of the tumor, including local site and/or distant metastasis. The primary endpoint was RFS analysis. The secondary endpoints were characterization, overall survival (OS) and prognostic factors of recurrence.

Results: Among 950 patients, 90 exhibited LAP criteria (9%). 55 met the inclusion criteria (median age: 53 years-old, 61% males, 14% with a germline mutation, 84% with a catecholamine excess). LAP was defined by 31 (56%) capsular invasions, 27 (49%) fat invasions, 6 (11%) positive lymph nodes and 22 (40%) vascular invasions. After a median follow-up of 54 months (range, 6-180), 12 patients (22%) had recurrences and 3 (5%) died of a metastatic disease. Median RFS was 115 months (range, 6-168). The recurrences were local in 2 patients, distant in 2 and both local and distant in 8 patients. Median OS of patients was not reached. Size above 6.5cm (p=0.019) and Ki-67>2% (p=0.028) were identified as independent significant prognostic factors in multivariate analysis.

Conclusions: LAP represents 9% of pheochromocytoma's population and is characterized by a metastatic behavior. This study paved the way of a future pathological TNM classification.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/clinem/dgab202DOI Listing
March 2021

DietSee: An on-hand, portable, strip-type biosensor for lipolysis monitoring via real-time amperometric determination of glycerol in blood.

Anal Chim Acta 2021 Apr 27;1155:338358. Epub 2021 Feb 27.

Inovarion, F-75005, Paris, France; LSee S.A.S., F-20090, Ajaccio, France. Electronic address:

Glycerol is a clinical biomarker of lipolysis that is mainly produced by adipose tissues. Blood glycerol content increases in pathological conditions such as metabolic and cardiovascular diseases or cancer cachexia, but also in response to energetic stress such as physical exercise. Accurate glycerol monitoring is therefore important in a range of healthcare contexts. However, current methods available for the quantification of glycerol are expensive, time-consuming, and require the extraction of plasma from blood, from which blood glycerol content is then extrapolated. Here, we report the development of a new point-of-care glycerometer device, DietSee, based on a strip-type biosensor that enables the quantification of glycerol directly from whole blood in 6 s. The performance of the biosensor was first evaluated using buffer solutions and spiked human and mouse plasma samples, and its response was compared with that of the gold-standard colorimetric method. The results obtained using DietSee correlated strongly with those from the reference method and demonstrated a linear response to glycerol levels across a wide range of concentrations (40-750 μM) that were representative of those in the human body. Next, the biosensor was validated using spiked human blood samples over a range of 30-55% hematocrit; it also demonstrated a strong correlation with reference measurements under these conditions (R = 0.97). In addition, the biosensor was only minimally affected by a variety of potential interferents (endogenous and exogenous) and was highly stable in storage (more than 2 years when strips were stored dry at 4 °C). Finally, we investigated the application of the biosensor to real-time monitoring of lipolysis and found that the DietSee is well adapted for this purpose in both human and mouse samples. To conclude, the novel DietSee glycerometer is a sensitive, selective, and rapid tool that enables characterization of the metabolic status of an individual by measuring the glycerol concentration from a single fingertip blood drop.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.aca.2021.338358DOI Listing
April 2021

Cholangiopathy aggravation is caused by VDR ablation and alleviated by VDR-independent vitamin D signaling in ABCB4 knockout mice.

Biochim Biophys Acta Mol Basis Dis 2021 04 6;1867(4):166067. Epub 2021 Jan 6.

Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Paris, France; AP-HP, Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis (CRMR, MIVB-H), Department of Hepatology, Saint-Antoine Hospital, Paris, France. Electronic address:

Background & Aims: Cholangiopathies are chronic liver diseases in which damaged cholangiocytes trigger a proinflammatory and profibrotic reaction. The nuclear vitamin D receptor (VDR) is highly expressed in cholangiocytes and exerts immune-regulatory functions in these cells. In the present study, we examined the protective function of VDR and other vitamin D signaling pathways in chronic cholangiopathy and cholangiocytes.

Methods: Vdr was invalidated in Abcb4 knockout mice, a widely used animal model of chronic cholangiopathy. The impact of vitamin D signaling on cholangiopathy features was examined in vivo and in cholangiocytes (primary and cell lines).

Results: Cholangiopathy features (i.e, cholestasis, ductular reaction and fibrosis) were aggravated in Vdr;Abcb4 double knockout mice compared to the Abcb4 simple knockout, and associated with an overexpression of proinflammatory factors. The proinflammatory phenotype of cholangiocytes was also exacerbated following VDR silencing in vitro. The expression of proinflammatory factors and the severity of cholangiopathy were reduced in the double knockout mice treated with the vitamin D analog calcipotriol or with vitamin D. In vitro, the inflammatory response to TNFα was significantly reduced by calcipotriol in biliary cells silenced for VDR, and this effect was abolished by co-silencing the plasma membrane receptor of vitamin D, protein disulfide-isomerase A3 (PDIA3).

Conclusions: Our results demonstrate an anti-inflammatory role of VDR signaling in cholangiocytes and cholangiopathy. They also provide evidence for PDIA3-mediated anti-inflammatory effects of vitamin D and vitamin D analog in these settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbadis.2020.166067DOI Listing
April 2021

Lamin-Related Congenital Muscular Dystrophy Alters Mechanical Signaling and Skeletal Muscle Growth.

Int J Mol Sci 2020 Dec 30;22(1). Epub 2020 Dec 30.

Center for Research in Myology, Sorbonne Université, INSERM UMRS_974, 75013 Paris, France.

Laminopathies are a clinically heterogeneous group of disorders caused by mutations in the gene, which encodes the nuclear envelope proteins lamins A and C. The most frequent diseases associated with mutations are characterized by skeletal and cardiac involvement, and include autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD), limb-girdle muscular dystrophy type 1B, and -related congenital muscular dystrophy (-CMD). Although the exact pathophysiological mechanisms responsible for -CMD are not yet understood, severe contracture and muscle atrophy suggest that mutations may impair skeletal muscle growth. Using human muscle stem cells (MuSCs) carrying -CMD mutations, we observe impaired myogenic fusion with disorganized cadherin/β catenin adhesion complexes. We show that skeletal muscle from -CMD mice is unable to hypertrophy in response to functional overload, due to defective fusion of activated MuSCs, defective protein synthesis and defective remodeling of the neuromuscular junction. Moreover, stretched myotubes and overloaded muscle fibers with -CMD mutations display aberrant mechanical regulation of the yes-associated protein (YAP). We also observe defects in MuSC activation and YAP signaling in muscle biopsies from -CMD patients. These phenotypes are not recapitulated in closely related but less severe EDMD models. In conclusion, combining studies in vitro, in vivo, and patient samples, we find that -CMD mutations interfere with mechanosignaling pathways in skeletal muscle, implicating A-type lamins in the regulation of skeletal muscle growth.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms22010306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795708PMC
December 2020

Epigenetic and metabolic reprogramming of SDH-deficient paragangliomas.

Endocr Relat Cancer 2020 12;27(12):R451-R463

PARCC, INSERM UMR970, Equipe Labellisée par la Ligue contre le Cancer, Paris, France.

Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors arising from the adrenal medulla or extra-adrenal paraganglia. Around 40% of all cases are caused by a germline mutation in a susceptibility gene, half of which being found in an SDHx gene (SDHA, SDHB, SDHC, SDHD or SDHAF2). They encode the four subunits and assembly factor of succinate dehydrogenase (SDH), a mitochondrial enzyme involved both in the tricarboxylic acid cycle and electron transport chain. SDHx mutations lead to the accumulation of succinate, which acts as an oncometabolite by inhibiting iron(II) and alpha-ketoglutarate-dependent dioxygenases thereby regulating the cell's hypoxic response and epigenetic processes. Moreover, SDHx mutations induce cell metabolic reprogramming and redox imbalance. Major discoveries in PPGL pathophysiology have been made since the initial discovery of SDHD gene mutations in 2000, improving the understanding of their biology and patient management. It indeed provides new opportunities for diagnostic tools and innovative therapeutic targets in order to improve the prognosis of patients affected by these rare tumors, in particular in the context of metastatic diseases associated with SDHB mutations. This review first describes an overview of the pathophysiology and then focuses on clinical implications of the epigenetic and metabolic reprogramming of SDH-deficient PPGL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1530/ERC-20-0346DOI Listing
December 2020

TET-Mediated Hypermethylation Primes SDH-Deficient Cells for HIF2α-Driven Mesenchymal Transition.

Cell Rep 2020 03;30(13):4551-4566.e7

Université de Paris, PARCC, INSERM, Equipe Labellisée par la Ligue contre le Cancer, 75015 Paris, France. Electronic address:

Loss-of-function mutations in the SDHB subunit of succinate dehydrogenase predispose patients to aggressive tumors characterized by pseudohypoxic and hypermethylator phenotypes. The mechanisms leading to DNA hypermethylation and its contribution to SDH-deficient cancers remain undemonstrated. We examine the genome-wide distribution of 5-methylcytosine and 5-hydroxymethylcytosine and their correlation with RNA expression in SDHB-deficient tumors and murine Sdhb cells. We report that DNA hypermethylation results from TET inhibition. Although it preferentially affects PRC2 targets and known developmental genes, PRC2 activity does not contribute to the DNA hypermethylator phenotype. We also prove, in vitro and in vivo, that TET silencing, although recapitulating the methylation profile of Sdhb cells, is not sufficient to drive their EMT-like phenotype, which requires additional HIF2α activation. Altogether, our findings reveal synergistic roles of TET repression and pseudohypoxia in the acquisition of metastatic traits, providing a rationale for targeting HIF2α and DNA methylation in SDH-associated malignancies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2020.03.022DOI Listing
March 2020

Lamin Mutations Cause Increased YAP Nuclear Entry in Muscle Stem Cells.

Cells 2020 03 27;9(4). Epub 2020 Mar 27.

INSERM UMRS_974, Centre for Research in Myology, Sorbonne Université, 75013 Paris, France.

Mutations in the gene, encoding the nuclear envelope A-type lamins, are responsible for muscular dystrophies, the most severe form being the -related congenital muscular dystrophy (L-CMD), with severe defects in myonucleus integrity. We previously reported that L-CMD mutations compromise the ability of muscle stem cells to modulate the yes-associated protein (YAP), a pivotal factor in mechanotransduction and myogenesis. Here, we investigated the intrinsic mechanisms by which lamins influence YAP subcellular distribution, by analyzing different conditions affecting the balance between nuclear import and export of YAP. In contrast to wild type (WT) cells, mutations failed to exclude YAP from the nucleus and to inactivate its transcriptional activity at high cell density, despite activation of the Hippo pathway. Inhibiting nuclear pore import abolished YAP nuclear accumulation in confluent mutant cells, thus showing persistent nuclear import of YAP at cell confluence. YAP deregulation was also present in congenital myopathy related to nesprin-1 mutation, but not in cells expressing the mutation, the adult form of lamin-related muscle dystrophy with reduced nuclear deformability. In conclusion, our data showed that L-CMD mutations increased YAP nuclear localization via an increased nuclear import and implicated YAP as a pathogenic contributor in muscle dystrophies caused by nuclear envelop defects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cells9040816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226749PMC
March 2020

An Emerin LEM-Domain Mutation Impairs Cell Response to Mechanical Stress.

Cells 2019 06 10;8(6). Epub 2019 Jun 10.

Laboratory of Structural Biology and Radiobiology, Institute for Integrative Biology of the Cell (CEA, CNRS, University Paris South), University Paris-Saclay, 91190 Gif-sur-Yvette, France.

Emerin is a nuclear envelope protein that contributes to genome organization and cell mechanics. Through its N-terminal LAP2-emerin-MAN1 (LEM)-domain, emerin interacts with the DNA-binding protein barrier-to-autointegration (BAF). Emerin also binds to members of the linker of the nucleoskeleton and cytoskeleton (LINC) complex. Mutations in the gene encoding emerin are responsible for the majority of cases of X-linked Emery-Dreifuss muscular dystrophy (X-EDMD). Most of these mutations lead to an absence of emerin. A few missense and short deletion mutations in the disordered region of emerin are also associated with X-EDMD. More recently, missense and short deletion mutations P22L, ∆K37 and T43I were discovered in emerin LEM-domain, associated with isolated atrial cardiac defects (ACD). Here we reveal which defects, at both the molecular and cellular levels, are elicited by these LEM-domain mutations. Whereas K37 mutation impaired the correct folding of the LEM-domain, P22L and T43I had no impact on the 3D structure of emerin. Surprisingly, all three mutants bound to BAF, albeit with a weaker affinity in the case of K37. In human myofibroblasts derived from a patient's fibroblasts, emerin ∆K37 was correctly localized at the inner nuclear membrane, but was present at a significantly lower level, indicating that this mutant is abnormally degraded. Moreover, SUN2 was reduced, and these cells were defective in producing actin stress fibers when grown on a stiff substrate and after cyclic stretches. Altogether, our data suggest that the main effect of mutation K37 is to perturb emerin function within the LINC complex in response to mechanical stress.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cells8060570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628311PMC
June 2019

CCAAT/enhancer binding protein delta (C/EBPδ) deficiency does not affect bleomycin-induced pulmonary fibrosis.

J Clin Transl Res 2018 Jul 21;3(Suppl 2):358-365. Epub 2018 Feb 21.

3 Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, the Netherlands.

Background: Idiopathic pulmonary fibrosis is a devastating fibrotic diffuse parenchymal lung disorder that remains refractory to pharmacological therapies. Therefore, novel treatments are urgently required. CCAAT/enhancer binding protein delta (C/EBPδ) is a transcription factor that mediates critical cellular functions in pathophysiology and which was recently suggested to be a key regulatory component in IPF. The purpose of this study was to prove or refute the importance of C/EBPδ in pulmonary fibrosis.

Methods: Pulmonary fibrosis was induced by intranasal instillation of bleomycin into wild-type and C/EBPδ deficient mice. At different time intervals after bleomycin instillation, fibrosis was assessed by hydroxyproline analysis, histochemistry and q-PCR for fibrotic marker expression.

Results: C/EBPδ deficient mice developed pulmonary fibrosis to a similar degree as wildtype mice as evident from similar Ashcroft scores, hydroxyproline levels and expression levels of collagen, fibronectin and α-smooth muscle actin at both 14 and 21 days after bleomycin instillation. The resolution of fibrosis, assessed at 48 days after bleomycin instillation, was also similar in wildtype and C/EBPδ deficient mice. In line with the lack of effect of C/EBPδ on fibrosis progression/resolution, macrophage recruitment and/or differentiation were also not different in wildtype or C/EBPδ deficient mice.

Conclusions: Overall, C/EBPδ does not seem to affect bleomycin-induced experimental pulmonary fibrosis and we challenge the importance of C/EBPδ in pulmonary fibrosis.

Relevance For Patients: This study shows that the transcription factor C/EBPδ does not play a major role in the development of pulmonary fibrosis. Pharmacological targeting of C/EBPδ is therefore not likely to have a beneficial effect for patients suffering from pulmonary fibrosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412614PMC
July 2018

18F-FDOPA PET/CT Uptake Parameters Correlate with Catecholamine Secretion in Human Pheochromocytomas.

Neuroendocrinology 2018 27;107(3):228-236. Epub 2018 Jun 27.

Aix-Marseille Université, INSERM, U1251, Marseille Medical Genetics and AP-HM, Department of Endocrinology, Hôpital de la Conception, Centre de Référence des Maladies Rares Hypophysaires HYPO, Marseille,

Background: 18F-FDOPA positron emission tomography/computed tomography (PET/CT) is a sensitive nuclear imaging technology for the diagnosis of pheochromocytomas (PHEO). However, its utility in determining predictive factors for the secretion of catecholamines remains poorly studied.

Methods: Thirty-nine histologically confirmed PHEO were included in this retrospective single-center study. Patients underwent 18F-FDOPA PET/CT before surgery, with an evaluation of several uptake parameters (standardized uptake values [SUVmax and SUVmean] and the metabolic burden [MB] calculated as follows: MB = SUVmean × tumor volume) and measurement of plasma and/or urinary metanephrine (MN), normetanephrine (NM), and chromogranin A. Thirty-five patients were screened for germline mutations in the RET, SDHx, and VHL genes. Once resected, primary cultures of 5 PHEO were used for real-time measurement of catecholamine release by carbon fiber amperometry.

Results: The MB of the PHEO positively correlated with 24-h urinary excretion of NM (r = 0.64, p < 0.0001), MN (r = 0.49, p = 0.002), combined MN and NM (r = 0.75, p < 0.0001), and eventually plasma free levels of NM (r = 0.55, p = 0.006). In the mutated patients (3 SDHD, 2 SDHB, 3 NF1, 1 VHL, and 3 RET), a similar correlation was observed between MB and 24-h urinary combined MN and NM (r = 0.86, p = 0.0012). For the first time, we demonstrate a positive correlation between the PHEO-to-liver SUVmax ratio and the mean number of secretory granule fusion events of the corresponding PHEO cells revealed by amperometric spikes (p = 0.01).

Conclusion: While the 18F-FDOPA PET/CT MB of PHEO strongly correlates with the concentration of MN, amperometric recordings suggest that 18F-FDOPA uptake could be enhanced by overactivity of catecholamine exocytosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000491578DOI Listing
January 2019

The computed tomography adrenal wash-out analysis properly classifies cortisol secreting adrenocortical adenomas.

Endocrine 2018 03 13;59(3):529-537. Epub 2018 Jan 13.

Department of Endocrinology, University Hospital of Nancy, Nancy, France.

Purpose: Adrenocortical lesions are characterized through imaging, hormonal and histopathological analysis. Our aim was to compare the radiological features of adrenocortical lesions with their cortisol-secreting status and histopathological Weiss score.

Methods: Seventy five patients operated between 2004 and 2016 in the University Hospital of Nancy for either adrenocortical carcinomas (ACC) or adrenocortical adenomas (ACA) were enrolled in this study. We collected cortisol parameters, Computed Tomography (CT) scans (unenhanced density, wash-out (WO) analysis) and F-Fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) datas. The histopathological Weiss score ultimately differentiates ACA (score ≤ 2) from ACC (score ≥ 3). One-way ANOVA, Fisher's exact and unpaired t tests were used for statistical analysis with significancy reached at p < 0.05.

Results: There were 23 ACC and 52 ACA with 40 patients (53%) who had an autonomous secretion of cortisol. On CT scan, ACC were larger compared to ACA (108 vs. 37 mm, p < 0.0001). A roughly similar proportion of cortisol-secreting (22/25) and non-secreting (15/19) ACA were atypical (i.e., unenhanced density value ≥ 10 Hounsfield Units [HU]), however 85% of cortisol-secreting vs. 40% of non-secreting ACA were classified as benigns by the relative WO analysis (p = 0.08). Likewise, there was a trend for a higher F-FDG uptake in cortisol-secreting ACA compared to non-secreting ACA (p = 0.053).

Conclusions: The relative adrenal WO analysis consolidates the benign nature of an ACA, especially in case of cortisol oversecretion, a condition known to compromise the diagnostic accuracy of the 10 HU unenhanced CT attenuation threshold.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12020-018-1522-7DOI Listing
March 2018

Human airway trypsin-like protease exerts potent, antifibrotic action in pulmonary fibrosis.

FASEB J 2018 03 3;32(3):1250-1264. Epub 2018 Jan 3.

INSERM, Unité 1552, Paris, France.

Idiopathic pulmonary fibrosis (IPF) is characterized by the deposition of excessive extracellular matrix and the destruction of lung parenchyma, resulting from an aberrant wound-healing response. Although IPF is often associated with an imbalance in protease activity, the mechanisms underlying the sustained repair mechanisms are not fully understood. Here, we addressed the role of the recently identified, membrane-anchored serine protease human airway trypsin-like protease (HAT). In the present study, we show that both HAT expression and activity were up-regulated in human IPF specimens. Next, adenoviral overexpression of HAT before bleomycin challenge attenuated lung injury as well as extracellular matrix deposition in the bleomycin-induced pulmonary fibrosis model. In vitro, HAT prevented specific fibrosis-associated responses in primary human pulmonary fibroblasts and induced the expression of mediators associated with the prostaglandin E2 pathway. Altogether, our findings suggested that HAT could have a protective role in IPF and other fibrotic lung disorders.-Menou, A., Flajolet, P., Duitmen, J., Justet, A., Moog, S., Jaillet, M., Tabèze, L., Solhonne, B., Garnier, M., Mal, H., Mordant, P., Castier, Y., Cazes, A., Sallenave, J.-M., Mailleux, A. A., Crestani, B. Human airway trypsin-like protease exerts potent, antifibrotic action in pulmonary fibrosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1096/fj.201700583RDOI Listing
March 2018