Matrix metalloproteinases contribute to kidney fibrosis in chronic kidney diseases

Zhao, Hong; Dong, Yanting; Tian, Xinggui; Tan, Thian Kui; Liu, Zhuo-la; Zhao, Ye; Zhang, Yun; Harris, David C.H.; Zheng, Guoping

doi:10.5527/wjn.v2.i3.84

Cited by 117 publications

(110 citation statements)

References 52 publications

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“…This raises the possibility that MMP-9 and TGF-␤ could participate in a contraction-dependent positive feedback loop that regulates fibroblast function. The potential for positive feedback between TGF-␤ and MMP-9 is further supported, since TGF-␤ can modulate release of MMP-9 (32,46). MMP-9 production by unstimulated fibroblasts is low.…”

Section: Discussionmentioning

confidence: 92%

Matrix metalloproteinase-9 activates TGF-β and stimulates fibroblast contraction of collagen gels

Kobayashi

Kim

Liu

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

172

128

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is a matrix-degrading enzyme implicated in many biological processes, including inflammation. It is produced by many cells, including fibroblasts. When cultured in three-dimensional (3D) collagen gels, fibroblasts contract the surrounding matrix, a function that is thought to model the contraction that characterizes both normal wound repair and fibrosis. The current study was designed to evaluate the role of endogenously produced MMP-9 in fibroblast contraction of 3D collagen gels. Fibroblasts from mice lacking expression of MMP-9 and human lung fibroblasts (HFL-1) transfected with MMP-9 smallinterfering RNA (siRNA) were used. Fibroblasts were cast into type I collagen gels and floated in culture medium with or without transforming growth factor (TGF)-␤1 for 5 days. Gel size was determined daily using an image analysis system. Gels made from MMP-9 siRNA-treated human fibroblasts contracted less than control fibroblasts, as did fibroblasts incubated with a nonspecific MMP inhibitor. Similarly, fibroblasts cultured from MMP-9-deficient mice contracted gels less than did fibroblasts from control mice. Transfection of the MMP-9-deficient murine fibroblasts with a vector expressing murine MMP-9 restored contractile activity to MMP-9-deficient fibroblasts. Inhibition of MMP-9 reduced active TGF-␤1 and reduced several TGF-␤1-driven responses, including activity of a Smad3 reporter gene and production of fibronectin. Because TGF-␤1 also drives fibroblast gel contraction, this suggests the mechanism for MMP-9 regulation of contraction is through the generation of active TGF-␤1. This study provides direct evidence that endogenously produced MMP-9 has a role in regulation of tissue contraction of 3D collagen gels mediated by fibroblasts. lung; repair; transforming growth factor-␤

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Section: Discussionmentioning

confidence: 92%

Matrix metalloproteinase-9 activates TGF-β and stimulates fibroblast contraction of collagen gels

Kobayashi

Kim

Liu

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

172

128

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“…The ECM, produced by fibroblasts and myofibroblasts (25,26), is degraded by MMP (20). TGF-β enhances the production of ECM by myofibroblasts (35)(36)(37).…”

Section: Equation For Tec Density (E)mentioning

confidence: 99%

“…PDGF and TGF-β transform fibroblasts to myofibroblasts (16,19), which together with fibroblasts produce ECM (25,26). Imbalance between MMP and its inhibitor TIMP facilitates the accumulation of ECM and formation of interstitial fibrosis (17,20).…”

mentioning

confidence: 99%

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Mathematical model of renal interstitial fibrosis

Hao¹,

Rovin²,

Friedman

2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance This paper deals with fibrosis of the kidney, a disease caused by inflammation, and so far there has been no way to diagnose and monitor the disease’s progression with noninvasive methods (the only way to determine the disease state is by biopsy, which cannot be frequently repeated). For this reason we developed a mathematical model of progression of renal fibrosis and validated it with biomarkers that were obtained from patients’ urine samples. We then used the model to show how antifibrosis drugs that are currently being developed for nonrenal fibrosis can be used to treat renal fibrosis.

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“…They, in turn, generate matrix metalloproteinases (MMPs) and pro-fibrotic cytokines, accordingly (8). MMPs, especially MMP-2 and MMP-9, secreted by macrophages and up-regulated by TGF-β1 in kidney tubular epithelial cells, have been shown to be pro-fibrotic by induction of tubular cells EMT (9). MMP-9 decays normal basement membrane collagen and postpones degradation and endorses gathering of extracellular matrix (10).…”

Section: Epithelial-mesenchymal Transitionmentioning

confidence: 99%

Epithelial and endothelial mesenchymal transition and their role in diabetic kidney disease

Dadras¹,

Sheikh²,

Khoshjou³

2017

J Renal Inj Prev

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Diabetes and its complications including diabetic nephropathy are spreading worldwide. On the other hand, pathophysiology of diabetic kidney disease and its modifiers have been studied broadly. This mini-review presents a couple of them, allocated to EMT and Endomt, briefly and to the point. Diabetic nephropathy (DN) is the main cause of end-stage renal disease. On the other hand, there are a couple of evidences, including human studies, which prove the role of epithelial mesenchymal transition (EMT) in pathophysiology of DN. EMT is characterized by loss of epithelial proteins and gain of mesenchymal markers. EMT is induced via three main conduit; TGFβ/Smad, integrin /ILK as well as Wnt/β-catenin pathways. Besides, numerous studies illustrated how drugs and agents can modify this phenomenon. On the other hand, endothelial mesenchymal transition (EndoMT) has a well-known role in pathophysiology of diabetic nephropathy which has been studied in animal and human. Here, several drugs and modifiers which have been studied to ffigure out if they can amend nature of EMT or EndoMT are reported briefly. Please cite this paper as:

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Matrix metalloproteinases contribute to kidney fibrosis in chronic kidney diseases

Cited by 117 publications

References 52 publications

Matrix metalloproteinase-9 activates TGF-β and stimulates fibroblast contraction of collagen gels

Matrix metalloproteinase-9 activates TGF-β and stimulates fibroblast contraction of collagen gels

Mathematical model of renal interstitial fibrosis

Epithelial and endothelial mesenchymal transition and their role in diabetic kidney disease

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