2009
DOI: 10.2353/ajpath.2009.080983
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Disruption of E-Cadherin by Matrix Metalloproteinase Directly Mediates Epithelial-Mesenchymal Transition Downstream of Transforming Growth Factor-β1 in Renal Tubular Epithelial Cells

Abstract: Epithelial-mesenchymal transition (EMT) plays an important role in organ fibrosis , including that of the kidney. Loss of E-cadherin expression is a hallmark of EMT; however , whether the loss of E-cadherin is a consequence or a cause of EMT remains unknown , especially in the renal system. In this study , we show that transforming growth factor (TGF)-␤1-induced EMT in renal tubular epithelial cells is dependent on proteolysis. Matrix metalloproteinase-mediated E-cadherin disruption led directly to tubular epi… Show more

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Cited by 210 publications
(191 citation statements)
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“…The role of MMPs as EMT inducers has been described in kidney, lung, ovary, oral, and mammary epithelium [52][53][54][55][56][57]. Their mechanism of action involves the processing and activation of pro-TGF-β in the ECM, as well as the direct proteolysis of E-cadherin [53,55,57].…”
Section: The Epithelium To Mesenchymal Transitionmentioning
confidence: 99%
“…The role of MMPs as EMT inducers has been described in kidney, lung, ovary, oral, and mammary epithelium [52][53][54][55][56][57]. Their mechanism of action involves the processing and activation of pro-TGF-β in the ECM, as well as the direct proteolysis of E-cadherin [53,55,57].…”
Section: The Epithelium To Mesenchymal Transitionmentioning
confidence: 99%
“…20 Recent studies from our group have demonstrated that MMP-9 itself is capable of inducing the entire course of tubular cell EMT via the disruption of E-cadherin/b-cateninmediated cell-to-cell adhesion complex, independent of epithelial cell-basement membrane disruption. 6,21 Moreover, results from our in vitro study has highlighted a prominent role and potentially an important source of MMP-9 from macrophages and TEC in tubular cell EMT induction, which has not previously been addressed in renal fibrosis. 6 Beside tubular cell EMT induction, MMP-9 is known to be capable of cleaving osteopontin (OPN), 22 a macrophage chemoattractant and macrophages are well known to have a role in renal fibrosis.…”
mentioning
confidence: 94%
“…[2][3][4][5] Tubular cell epithelialmesenchymal transition (EMT) is the transition of TEC into cells of mesenchymal phenotype, where TEC lose their epithelial characteristics and acquire a mesenchymal phenotype with the ability to secrete ECM. While EMT of primary TEC or cell lines in response to transforming growth factor-b1 (TGF-b1) has been well established, [6][7][8][9] the exact contribution of tubular cell EMT to kidney fibrosis is still under debate. [10][11][12][13] Iwano et al 3 demonstrated that EMT of TEC contributed to over a third of myofibroblasts in renal fibrosis by using proximal TEC genetically tagged mice in a UUO model.…”
mentioning
confidence: 99%
“…α-smooth muscle actin, fibroblast-specific protein and vimentin, a process that culminates in cytoskeletal remodelling and disruption of the tubular basement membrane [13,14]. Loss of cell adhesion, associated with reduced E-cadherin levels, represents a pivotal step in those early phenotypical and morphological changes previously observed in response to TGF-β1-induced tubular injury [15]. Cadherins have a central role in forming the multi-protein adherens junction that links cell-to-cell contact to the actin cytoskeleton and various other signalling molecules [16].…”
Section: Introductionmentioning
confidence: 99%