58 results match your criteria soluble biglycan


Biglycan reduces body weight by regulating food intake in mice and improves glucose metabolism through AMPK/AKT dual pathways in skeletal muscle.

FASEB J 2021 08;35(8):e21794

Interdisciplinary Program in Precision Public Health, Korea University, Seoul, Republic of Korea.

While biglycan (BGN) is suggested to direct diverse signaling cascades, the effects of soluble BGN as a ligand on metabolic traits have not been studied. Herein, we tested the effects of BGN on obesity in high-fat diet (HFD)-induced obese animals and glucose metabolism, with the underlying mechanism responsible for observed effects in vitro. Our results showed that BGN administration (1 mg/kg body weight, intraperitoneally) significantly prevented HFD-induced obesity, and this was mainly attributed to reduced food intake. Read More

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Biglycan: an emerging small leucine-rich proteoglycan (SLRP) marker and its clinicopathological significance.

Mol Cell Biochem 2021 Jun 28. Epub 2021 Jun 28.

Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, 110 029, India.

Extracellular matrix (ECM) plays an important role in the structural organization of tissue and delivery of external cues to the cell. Biglycan, a class I small leucine-rich proteoglycans (SLRP), is a key component of the ECM that participates in scaffolding the collagen fibrils and mediates cell signaling. Dysregulation of biglycan expression can result in wide range of clinical conditions such as metabolic disorder, inflammatory disorder, musculoskeletal defects and malignancies. Read More

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Biglycan: A regulator of hepatorenal inflammation and autophagy.

Matrix Biol 2021 06 10;100-101:150-161. Epub 2021 Jun 10.

Institute of Pharmacology and Toxicology, Goethe University, Frankfurt, Germany. Electronic address:

Soluble biglycan, a small leucine-rich proteoglycan, plays a significant role in several pathologies as it has emerged as an extracellular matrix-derived danger-associated molecular pattern. Biglycan is released from the extracellular matrix in response to tissue injury and, as a canonical danger signal, interacts with innate immune receptors, Toll-like receptors 2 and 4, thereby triggering a sustained inflammatory response. Recent evidence indicates that biglycan acts as a molecular switch between inflammation and autophagy by a specific interaction with the Toll-like co-receptor CD14 and CD44, respectively. Read More

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A functional outside-in signaling network of proteoglycans and matrix molecules regulating autophagy.

Matrix Biol 2021 06 7;100-101:118-149. Epub 2021 Apr 7.

Department of Pathology, Anatomy, and Cell Biology, and the Translational Cellular Oncology Program, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania, USA. Electronic address:

Proteoglycans and selected extracellular matrix constituents are emerging as intrinsic and critical regulators of evolutionarily conversed, intracellular catabolic pathways. Often, these secreted molecules evoke sustained autophagy in a variety of cell types, tissues, and model systems. The unique properties of proteoglycans have ushered in a paradigmatic shift to broaden our understanding of matrix-mediated signaling cascades. Read More

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Multi-omic signatures of atherogenic dyslipidaemia: pre-clinical target identification and validation in humans.

J Transl Med 2021 01 6;19(1). Epub 2021 Jan 6.

Department of Biochemistry, Faculty of Medicine, Medical University of Gdansk, 1 Debinki St, 80-211, Gdansk, Poland.

Background: Dyslipidaemia is a major risk factor for atherosclerosis and cardiovascular diseases. The molecular mechanisms that translate dyslipidaemia into atherogenesis and reliable markers of its progression are yet to be fully elucidated. To address this issue, we conducted a comprehensive metabolomic and proteomic analysis in an experimental model of dyslipidaemia and in patients with familial hypercholesterolemia (FH). Read More

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January 2021

Communications via the Small Leucine-rich Proteoglycans: Molecular Specificity in Inflammation and Autoimmune Diseases.

J Histochem Cytochem 2020 12 6;68(12):887-906. Epub 2020 Jul 6.

Pharmazentrum Frankfurt/ZAFES, Institut für Allgemeine Pharmakologie und Toxikologie, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt am Main, Frankfurt am Main, Germany.

Inflammation is a highly regulated biological response of the immune system that is triggered by assaulting pathogens or endogenous alarmins. It is now well established that some soluble extracellular matrix constituents, such as small leucine-rich proteoglycans (SLRPs), can act as danger signals and trigger aseptic inflammation by interacting with innate immune receptors. SLRP inflammatory signaling cascade goes far beyond its canonical function. Read More

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December 2020

Biglycan regulates neuroinflammation by promoting M1 microglial activation in early brain injury after experimental subarachnoid hemorrhage.

J Neurochem 2020 02 15;152(3):368-380. Epub 2019 Dec 15.

Department of Neurosurgery, the Affiliated Hospital of Southwest Medical University, Luzhou, China.

Neuroinflammation can be caused by various factors in early brain injury after subarachnoid hemorrhage (SAH). One of the most important features of this process is M1 microglial activation. In turn, the TLR4/NF-κB pathway plays an essential role in activating M1 phenotypic microglia. Read More

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February 2020

Danger matrix molecules orchestrate CD14/CD44 signaling in cancer development.

Semin Cancer Biol 2020 05 11;62:31-47. Epub 2019 Aug 11.

Pharmazentrum Frankfurt, Institut für Allgemeine Pharmakologie und Toxikologie, Goethe University, Frankfurt am Main, Germany. Electronic address:

The tumor matrix together with inflammation and autophagy are crucial regulators of cancer development. Embedded in the tumor stroma are numerous proteoglycans which, in their soluble form, act as danger-associated molecular patterns (DAMPs). By interacting with innate immune receptors, the Toll-like receptors (TLRs), DAMPs autonomously trigger aseptic inflammation and can regulate autophagy. Read More

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DAMPening sterile inflammation of the kidney.

Kidney Int 2019 03;95(3):489-491

Institute of Experimental Immunology, University Clinic of Bonn, Rheinische Friedrich Wilhelm University, Bonn, Germany. Electronic address:

Renal ischemia reperfusion injury (IRI) is a serious cause of acute kidney injury (AKI). Danger-associated-molecular pattern molecules (DAMPs) are thought to promote IRI by initiating immune cell infiltration and driving disease progression, but the underlying pathophysiological mechanisms are mainly unclear. Poluzzi et al. Read More

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Breaking down chronic inflammatory diseases: the role of biglycan in promoting a switch between inflammation and autophagy.

FEBS J 2019 08 27;286(15):2965-2979. Epub 2019 Feb 27.

Pharmazentrum Frankfurt/ZAFES, Institut für Allgemeine Pharmakologie und Toxikologie, Klinikum der Goethe-Universität, Frankfurt am Main, Germany.

It is well established that biglycan, a small leucine-rich proteoglycan, acts as an extracellular matrix-derived danger signal in its soluble form. By binding to innate immunity Toll-like receptors (TLR) 2 and 4, biglycan initiates and perpetuates the inflammatory response. Previous work has conveyed that biglycan's role in inflammation extends far beyond its function as a canonical danger signal. Read More

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Enhancement of tenogenic differentiation of rat tendon-derived stem cells by biglycan.

J Cell Physiol 2019 Feb 4. Epub 2019 Feb 4.

Laboratory of Stem Cell and Tissue Engineering, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, People's Republic of China.

Biglycan (BGN) has been identified as one of the critical components of the tendon-derived stem cells (TDSCs) niche and may be related to tendon formation. However, so far, no study has demonstrated whether the soluble BGN could induce the tenogenic differentiation of TDSCs in vitro. The aim of this study was to investigate the effect of BGN on the tenogenic differentiation of TDSCs. Read More

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February 2019

Biglycan evokes autophagy in macrophages via a novel CD44/Toll-like receptor 4 signaling axis in ischemia/reperfusion injury.

Kidney Int 2019 03 31;95(3):540-562. Epub 2019 Jan 31.

Pharmazentrum Frankfurt/ZAFES, Institut für Allgemeine Pharmakologie und Toxikologie, Klinikum der JW Goethe-Universität Frankfurt am Main, Frankfurt, Germany. Electronic address:

Biglycan, a small leucine-rich proteoglycan, acts as a danger signal and is classically thought to promote macrophage recruitment via Toll-like receptors (TLR) 2 and 4. We have recently shown that biglycan signaling through TLR 2/4 and the CD14 co-receptor regulates inflammation, suggesting that TLR co-receptors may determine whether biglycan-TLR signaling is pro- or anti-inflammatory. Here, we sought to identify other co-receptors and characterize their impact on biglycan-TLR signaling. Read More

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Biglycan is a new high-affinity ligand for CD14 in macrophages.

Matrix Biol 2019 04 17;77:4-22. Epub 2018 May 17.

Pharmazentrum Frankfurt, Institut für Allgemeine Pharmakologie und Toxikologie, Klinikum der Goethe-Universität Frankfurt am Main, Frankfurt am Main 60590, Germany. Electronic address:

Sterile inflammation is a therapeutic target in many diseases where it represents an important initiator of disease progression. However, the detailed mechanisms underlying its evolution and biological relevance are not yet completely elucidated. Biglycan, a prototype extracellular matrix-derived damage-associated molecular pattern, mediates sterile inflammation in macrophages through Toll-like receptor (TLR) 2 and/or TLR4-dependent signaling pathways. Read More

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The proteoglycan biglycan mediates inflammatory response by activating TLR-4 in human chondrocytes: Inhibition by specific siRNA and high polymerized Hyaluronan.

Arch Biochem Biophys 2018 02 13;640:75-82. Epub 2018 Jan 13.

Department of Clinical and Experimental Medicine, University of Messina, Policlinico Universitario, 98125 Messina, Italy. Electronic address:

Cartilage degeneration are hallmarks of wear, tear, mechanical and inflammatory damage of the joint cartilage. Tissue degradation as well as compromising the integrity and function of the organ, produces different intermediates, directly able to stimulate further inflammatory effect, therefore, amplifying the inflammation response. Biglycan is a soluble component of the extracellular matrix that is released during tissue injury. Read More

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February 2018

Small Leucine-Rich Proteoglycans in Renal Inflammation: Two Sides of the Coin.

J Histochem Cytochem 2018 04 1;66(4):261-272. Epub 2018 Jan 1.

Pharmazentrum Frankfurt/ZAFES, Institut für Allgemeine Pharmakologie und Toxikologie, Klinikum der JW Goethe-Universität Frankfurt am Main, Germany.

It is now well-established that members of the small leucine-rich proteoglycan (SLRP) family act in their soluble form, released proteolytically from the extracellular matrix (ECM), as danger-associated molecular patterns (DAMPs). By interacting with Toll-like receptors (TLRs) and the inflammasome, the two SLRPs, biglycan and decorin, autonomously trigger sterile inflammation. Recent data indicate that these SLRPs, besides their conventional role as pro-inflammatory DAMPs, additionally trigger anti-inflammatory signaling pathways to tightly control inflammation. Read More

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Biglycan, a novel trigger of Th1 and Th17 cell recruitment into the kidney.

Matrix Biol 2018 08 15;68-69:293-317. Epub 2017 Dec 15.

Pharmazentrum Frankfurt, Institut für Allgemeine Pharmakologie und Toxikologie, Goethe-Universität, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. Electronic address:

Th1 and Th17 cells, T helper (Th) subtypes, are key inducers of renal fibrosis. The molecular mechanisms of their recruitment into the kidney, however, are not well understood. Here, we show that biglycan, a proteoglycan of the extracellular matrix, acting in its soluble form as a danger signal, stimulates autonomously the production of Th1 and Th17 chemoattractants CXCL10 and CCL20 in macrophages. Read More

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Hair Germ Model In Vitro via Human Postnatal Keratinocyte-Dermal Papilla Interactions: Impact of Hyaluronic Acid.

Stem Cells Int 2017 10;2017:9271869. Epub 2017 Oct 10.

Laboratory of Cell Biology, N.K. Koltzov Institute of Developmental Biology, 26 Vavilov St., Moscow 119334, Russia.

Hair follicle (HF) reconstruction is a promising field in alopecia treatment and human HF development research. Here, we combined postnatal human dermal papilla (DP) cells and skin epidermal keratinocytes (KCs) in a hanging drop culture to develop an artificial HF germ. The method is based on DP cell hair-inducing properties and KC self-organization. Read More

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October 2017

Thyroxine Increases Collagen Type II Expression and Accumulation in Scaffold-Free Tissue-Engineered Articular Cartilage.

Tissue Eng Part A 2018 03 7;24(5-6):369-381. Epub 2017 Jul 7.

1 Department of Biomedical Engineering, Case Western Reserve University , Cleveland, Ohio.

Low collagen accumulation in the extracellular matrix is a pressing problem in cartilage tissue engineering, leading to a low collagen-to-glycosaminoglycan (GAG) ratio and poor mechanical properties in neocartilage. Soluble factors have been shown to increase collagen content, but may result in a more pronounced increase in GAG content. Thyroid hormones have been reported to stimulate collagen and GAG production, but reported outcomes, including which specific collagen types are affected, are variable throughout the literature. Read More

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Biglycan- and Sphingosine Kinase-1 Signaling Crosstalk Regulates the Synthesis of Macrophage Chemoattractants.

Int J Mol Sci 2017 Mar 9;18(3). Epub 2017 Mar 9.

Pharmazentrum Frankfurt, Institut für Allgemeine Pharmakologie und Toxikologie, Klinikum der Goethe Universität, Theodor-Stern-Kai 7, Frankfurt am Main 60590, Germany.

In its soluble form, the extracellular matrix proteoglycan biglycan triggers the synthesis of the macrophage chemoattractants, chemokine (C-C motif) ligand CCL2 and CCL5 through selective utilization of Toll-like receptors (TLRs) and their adaptor molecules. However, the respective downstream signaling events resulting in biglycan-induced CCL2 and CCL5 production have not yet been defined. Here, we show that biglycan stimulates the production and activation of sphingosine kinase 1 (SphK1) in a TLR4- and Toll/interleukin (IL)-1R domain-containing adaptor inducing interferon (IFN)-β (TRIF)-dependent manner in murine primary macrophages. Read More

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Proteoglycan neofunctions: regulation of inflammation and autophagy in cancer biology.

FEBS J 2017 01 7;284(1):10-26. Epub 2016 Dec 7.

Cancer Cell Biology and Signaling Program, Department of Pathology, Anatomy and Cell Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.

Inflammation and autophagy have emerged as prominent issues in the context of proteoglycan signaling. In particular, two small, leucine-rich proteoglycans, biglycan and decorin, play pivotal roles in the regulation of these vital cellular pathways and, as such, are intrinsically involved in cancer initiation and progression. In this minireview, we will address novel functions of biglycan and decorin in inflammation and autophagy, and analyze new emerging signaling events triggered by these proteoglycans, which directly or indirectly modulate these processes. Read More

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January 2017

A novel biological function of soluble biglycan: Induction of erythropoietin production and polycythemia.

Glycoconj J 2017 06 6;34(3):393-404. Epub 2016 Sep 6.

Pharmazentrum Frankfurt, Institut für Allgemeine Pharmakologie und Toxikologie, Klinikum der Goethe-Universität Frankfurt am Main, Frankfurt am Main, Germany.

Secondary polycythemia, a disease characterized by a selective increase in circulating mature erythrocytes, is caused by enhanced erythropoietin (Epo) concentrations triggered by hypoxia-inducible factor-2α (HIF-2α). While mechanisms of hypoxia-dependent stabilization of HIF-2α protein are well established, data regarding oxygen-independent regulation of HIF-2α are sparse. In this study, we generated a novel transgenic mouse model, in which biglycan was constitutively overexpressed and secreted by hepatocytes (BGN ), thereby providing a constant source of biglycan released into the blood stream. Read More

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Enhanced biglycan gene expression in the adipose tissues of obese women and its association with obesity-related genes and metabolic parameters.

Sci Rep 2016 07 28;6:30609. Epub 2016 Jul 28.

Department of General Surgery, Inha University, College of Medicine, Incheon, Korea.

Extracellular matrix (ECM) remodeling dynamically occurs to accommodate adipose tissue expansion during obesity. One non-fibrillar component of ECM, biglycan, is released from the matrix in response to tissue stress; the soluble form of biglycan binds to toll-like receptor 2/4 on macrophages, causing proinflammatory cytokine secretion. To investigate the pattern and regulatory properties of biglycan expression in human adipose tissues in the context of obesity and its related diseases, we recruited 21 non-diabetic obese women, 11 type 2 diabetic obese women, and 59 normal-weight women. Read More

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Soluble biglycan: a potential mediator of cartilage degradation in osteoarthritis.

Arthritis Res Ther 2015 Dec 24;17:379. Epub 2015 Dec 24.

Department of Rheumatology, University of Helsinki and Helsinki University (Central) Hospital, Helsinki, Finland.

Background: Soluble biglycan (sBGN) and soluble decorin (sDCN), are two closely related essential components of extracellular matrix which both have been shown to possess proinflammatory properties. We studied whether sBGN or sDCN were present in synovial fluid (SF) of osteoarthritis (OA) or rheumatoid arthritis (RA) patients and studied sBGN or sDCN potential role in the degradation of OA cartilage.

Methods: SF obtained from meniscus tear, OA, and RA patients were analysed for sBGN and sDCN using enzyme-linked immunosorbent assays. Read More

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December 2015

Bimodal role of NADPH oxidases in the regulation of biglycan-triggered IL-1β synthesis.

Matrix Biol 2016 Jan 12;49:61-81. Epub 2015 Dec 12.

Pharmazentrum Frankfurt, Institut für Allgemeine Pharmakologie und Toxikologie, Klinikum der Goethe-Universität Frankfurt am Main, Frankfurt am Main, Germany. Electronic address:

Biglycan, a ubiquitous proteoglycan, acts as a danger signal when released from the extracellular matrix. As such, biglycan triggers the synthesis and maturation of interleukin-1β (IL-1β) in a Toll-like receptor (TLR) 2-, TLR4-, and reactive oxygen species (ROS)-dependent manner. Here, we discovered that biglycan autonomously regulates the balance in IL-1β production in vitro and in vivo by modulating expression, activity and stability of NADPH oxidase (NOX) 1, 2 and 4 enzymes via different TLR pathways. Read More

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January 2016

Decorin is an autophagy-inducible proteoglycan and is required for proper in vivo autophagy.

Matrix Biol 2015 Oct 4;48:14-25. Epub 2015 Sep 4.

Department of Pathology, Anatomy and Cell Biology, and the Cancer Cell Biology and Signaling Program, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA. Electronic address:

We have recently discovered that soluble extracellular matrix constituents regulate autophagy via an outside-in signaling pathway. Decorin, a secreted proteoglycan, evokes autophagy in endothelial cells and mitophagy in breast carcinoma cells. However, it is not known whether decorin expression can be regulated by autophagic stimuli such as mTOR inhibition or nutrient deprivation. Read More

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October 2015

BMP-2 and TGF-β1 mediate biglycan-induced pro-osteogenic reprogramming in aortic valve interstitial cells.

J Mol Med (Berl) 2015 Apr 22;93(4):403-12. Epub 2014 Nov 22.

Department of Surgery, University of Colorado Denver, Box C-320, 12700 E 19th Avenue, Aurora, CO, 80045, USA.

Unlabelled: Biglycan accumulates in aortic valves affected by calcific aortic valve disease (CAVD), and soluble biglycan upregulates BMP-2 expression in human aortic valve interstitial cells (AVICs) via Toll-like receptor (TLR) 2 and induces AVIC pro-osteogenic reprogramming, characterized by elevated pro-osteogenic activities. We sought to identify the factors responsible for biglycan-induced pro-osteogenic reprogramming in human AVICs. Treatment of AVICs with recombinant biglycan induced the secretion of BMP-2 and TGF-β1, but not BMP-4 or BMP-7. Read More

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Combined antiretroviral therapy attenuates hepatic extracellular matrix remodeling in HIV patients assessed by novel protein fingerprint markers.

AIDS 2014 Sep;28(14):2081-90

Objectives: Combined antiretroviral therapy (cART) attenuates hepatic fibrosis in hepatitis C virus and HIV coinfected patients. However, the role of HIV or cART on hepatic fibrosis in HIV monoinfection is discussed controversially. During liver fibrosis, matrix metalloproteinases (MMPs) degrade extracellular matrix (ECM) proteins into small soluble fragments, which reflect hepatic remodeling processes. Read More

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September 2014

Soluble biglycan as a biomarker of inflammatory renal diseases.

Int J Biochem Cell Biol 2014 Sep 1;54:223-35. Epub 2014 Aug 1.

Pharmazentrum Frankfurt/ZAFES, Institut für Allgemeine Pharmakologie und Toxikologie, Klinikum der Goethe-Universität Frankfurt am Main, Frankfurt am Main, Germany. Electronic address:

Chronic renal inflammation is often associated with a progressive accumulation of various extracellular matrix constituents, including several members of the small leucine-rich proteoglycan (SLRP) gene family. It is becoming increasingly evident that the matrix-unbound SLRPs strongly regulate the progression of inflammation and fibrosis. Soluble SLRPs are generated either via partial proteolytic processing of collagenous matrices or by de novo synthesis evoked by stress or injury. Read More

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September 2014

Soluble biglycan induces the production of ICAM-1 and MCP-1 in human aortic valve interstitial cells through TLR2/4 and the ERK1/2 pathway.

Inflamm Res 2014 Sep 30;63(9):703-10. Epub 2014 May 30.

Department of Surgery, University of Colorado Denver, 12700 E 19th Avenue, Box C-320, Aurora, CO, 80045, USA.

Objective: Mononuclear cell infiltration in valvular tissue is one of the characteristics in calcific aortic valve disease. The inflammatory responses of aortic valve interstitial cells (AVICs) play an important role in valvular inflammation. However, it remains unclear what may evoke AVIC inflammatory responses. Read More

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September 2014

Biglycan-triggered TLR-2- and TLR-4-signaling exacerbates the pathophysiology of ischemic acute kidney injury.

Matrix Biol 2014 Apr 28;35:143-51. Epub 2014 Jan 28.

Pharmazentrum Frankfurt, Institut für Allgemeine Pharmakologie und Toxikologie/ZAFES, Klinikum der JW Goethe-Universität, Frankfurt am Main, Germany. Electronic address:

Exacerbated inflammation in renal ischemia-reperfusion injury, the major cause of intrinsic acute renal failure, is a key trigger of kidney damage. During disease endogenous danger signals stimulate innate immune cells via Toll-like receptors (TLR)-2 and -4 and accelerate inflammatory responses. Here we show that production of soluble biglycan, a small leucine-rich proteoglycan, is induced during reperfusion and that it functions as endogenous agonist of TLR-2/4. Read More

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