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      Progressive Renal Disease: Fibroblasts, Extracellular Matrix, and Integrins

      Cardiorenal Medicine
      S. Karger AG
      Fibrosis, Interstitital fibroblasts, Extracellular matrix, Integrins

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          Progressive renal disease is characterized by expansion of the tubulo-interstitium and accumulation of extracellular matrix within this tissue compartment. Interstitial fibroblasts are the primary producers of the interstitial matrix, and in the evolution of tubulo-interstitial fibrosis these cells undergo changes, namely increased proliferation, differentiation to myofibroblasts, and altered extracellular matrix metabolism, all of which, in other cell types, have been shown to be regulated by the major family of extracellular matrix receptors, the integrins. In the normal kidney, interstitial fibroblasts express α<sub>1</sub>, α<sub>4</sub>, α<sub>5</sub>, and β<sub>1</sub> integrins, and fibrosis is associated with increased expression of α<sub>1</sub>, α<sub>2</sub>, α<sub>5</sub>, α<sub>v</sub>, and β<sub>1</sub> integrins. In particular, α<sub>5</sub>, β<sub>1</sub>, and α<sub>v</sub> are suggested to be linked with the fibrotic process. In vitro, renal fibroblasts express a similar range of integrins, and ligation of selected receptors is associated with specific functions. Ligation of α<sub>6</sub> stimulates proliferation, while α<sub>5</sub> promotes expression of myofibroblastic phenotype, and β<sub>1</sub> integrin has been implicated in cell contraction. Recent studies suggest that renal fibroblasts also express the non-integrin matrix receptors, discoidin domain receptors, and that changes in activation of these receptors may be associated with fibrogenic events. Thus the current, albeit limited, data suggest an important role for receptors for extracellular matrix molecules in the pathogenesis of progressive renal fibrosis.

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          Most cited references17

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          Integrin αvβ3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels

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            Localization of Matrix Metalloproteinase MMP-2 to the Surface of Invasive Cells by Interaction with Integrin αvβ3

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              Identification and characterization of a fibroblast marker: FSP1

              F Strutz (1995)

                Author and article information

                Nephron Exp Nephrol
                Cardiorenal Medicine
                S. Karger AG
                April 1999
                23 April 1999
                : 7
                : 2
                : 167-177
                Department of Medicine, Royal Free and University College Medical School, London, UK
                20597 Exp Nephrol 1999;7:167–177
                © 1999 S. Karger AG, Basel

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                Page count
                Figures: 1, Tables: 1, References: 94, Pages: 11
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/20597
                Self URI (text/html): https://www.karger.com/Article/FullText/20597
                Self URI (journal page): https://www.karger.com/SubjectArea/Nephrology

                Cardiovascular Medicine,Nephrology
                Integrins,Extracellular matrix,Interstitital fibroblasts,Fibrosis


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