Myofibroblast differentiation and survival in fibrotic disease.
Myofibroblast differentiation and survival in fibrotic disease.
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DOI：
10.1017/s1462399411001967
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发表时间：
2011-08-23
影响因子：
6.2
通讯作者：
Hagood JS
中科院分区：
文献类型：
--
作者：
Kis K;Liu X;Hagood JS
在伤口愈合期间，称为肌成纤维细胞的收缩性成纤维细胞调节肉芽组织的形成和收缩;然而，病理性和持续性肌成纤维细胞活化，例如发生在增生性瘢痕或组织纤维化中，导致功能丧失。许多杰出的评论概述了肌成纤维细胞的细胞和分子特征，以及它们在各种疾病中的作用。本文就肌成纤维细胞的起源及其在纤维化组织中的分化和存活的影响因素作一综述。肺纤维化用于说明许多关键点，但也包括来自其他组织和模型的示例。肌成纤维细胞主要来自组织驻留的成纤维细胞，但也来自上皮细胞、内皮细胞或其他间充质前体细胞。它们的分化受到细胞因子、生长因子、细胞外基质组成和硬度以及细胞表面分子如蛋白聚糖和THY 1等因素的影响。这些效应中有许多是由细胞收缩调节的。肌成纤维细胞抵抗程序性细胞死亡，促进其在纤维化组织中的积累。肌成纤维细胞抗凋亡的原因正在进行中的调查，但许多相同的刺激，调节其分化的参与。氧化应激、WNT - β-catenin通路和PPARγ对肌成纤维细胞分化和存活的贡献越来越受到重视。
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 - β-catenin pathway and PPARγ to myofibroblast differentiation and survival are increasingly appreciated.