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2011 ; 13
(ä): e27
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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
PMID21861939
show ga
During wound healing, contractile fibroblasts called myofibroblasts regulate the
formation and contraction of granulation tissue; however, pathological and
persistent myofibroblast activation, which occurs in hypertrophic scars or tissue
fibrosis, results in a loss of function. Many reviews outline the cellular and
molecular features of myofibroblasts and their roles in a variety of diseases.
This review focuses on the origins of myofibroblasts and the factors that 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 originate mostly from
tissue-resident fibroblasts, and also from epithelial and 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, which promotes 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.