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Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Expert+Rev+Mol+Med 2011 ; 13 (ä): e27 Nephropedia Template TP
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MYOFIBROBLAST DIFFERENTIATION AND SURVIVAL IN FIBROTIC DISEASE #MMPMID21861939
Kis K; Liu X; Hagood JS
Expert Rev Mol Med 2011[Aug]; 13 (ä): e27 PMID21861939show ga
During wound healing, contractile fibroblasts called myofibroblasts regulate the formation and contraction of granulation tissue; however, pathological and persistent myofibroblast activation, such as occurs in hypertrophic scars or tissue fibrosis, results in loss of function. Many outstanding reviews outline cellular and molecular features of myofibroblasts, and their roles in a variety of diseases. This review will focus on the origins of myofibroblasts and the factors which control their differentiation and prolonged survival in fibrotic tissues. Pulmonary fibrosis is used to illustrate many key points, but examples from other tissues and models are also included. Myofibroblasts emerge mostly from tissue-resident fibroblasts but also from epithelial, endothelial cells or other mesenchymal precursors. Their differentiation is influenced by cytokines, growth factors, extracellular matrix composition and stiffness, and cell surface molecules such as proteoglycans and THY1, among other factors. Many of these effects are modulated by cell contraction. Myofibroblasts resist programmed cell death, promoting their accumulation in fibrotic tissues. The cause of resistance to apoptosis in myofibroblasts is under ongoing investigation, but many of the same stimuli that regulate their differentiation are involved. The contributions of oxidative stress, the WNT - ?-catenin pathway and PPAR? to myofibroblast differentiation and survival are increasingly appreciated.