Department of Pediatrics, Division of Respiratory Medicine, University of California-San Diego, San Diego, CA, USA.
Expert Rev Mol Med. 2011 Aug 23;13:e27. doi: 10.1017/S1462399411001967.
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-β-catenin pathway and PPARγ to myofibroblast differentiation and survival are increasingly appreciated.
在伤口愈合过程中，收缩性成纤维细胞（称为肌成纤维细胞）调节肉芽组织的形成和收缩；然而，在肥大性瘢痕或组织纤维化中发生的病理性和持续性肌成纤维细胞激活会导致功能丧失。许多综述概述了肌成纤维细胞的细胞和分子特征及其在各种疾病中的作用。本综述重点介绍了肌成纤维细胞的起源，以及控制其在纤维化组织中分化和延长存活的因素。肺纤维化被用来举例说明许多要点，但也包括来自其他组织和模型的例子。肌成纤维细胞主要来源于组织驻留的成纤维细胞，也来源于上皮细胞和内皮细胞或其他间充质前体。它们的分化受细胞因子、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 THY1 等）等因素的影响。其中许多作用都受到细胞收缩的调节。肌成纤维细胞抵抗程序性细胞死亡，这促进了它们在纤维化组织中的积累。肌成纤维细胞抗细胞凋亡的原因正在研究中，但调节其分化的许多相同刺激因素也参与其中。氧化应激、WNT-β-连环蛋白途径和 PPARγ 对肌成纤维细胞分化和存活的贡献越来越受到重视。
