Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-2200, USA.
Proc Am Thorac Soc. 2012 Jul;9(3):148-52. doi: 10.1513/pats.201201-011AW.
Tissue injury incites a repair response with a key mesenchymal component that provides the essential connective tissue for subsequent regeneration or pathological fibrosis. The fibroblast is the major mesenchymal cell type to be implicated in this connective tissue response, and it is in its activated or differentiated form that it participates in the repair process. The myofibroblast represents such an activated mesenchymal cell and is a key source of extracellular matrix and inflammatory/fibrogenic cytokines as well as participating in wound contraction. Although successful healing results in gradual disappearance of myofibroblasts, their persistence is associated with chronic and progressive fibrosis. Thus, elucidation of the mechanism involved in the genesis of the myofibroblast should provide insight into both pathogenesis of chronic fibrotic diseases and therapeutic strategies for their management and control. Although the fibroblast is a well-documented progenitor cell for the myofibroblast, recent studies have suggested additional precursor cells that have the potential to give rise to the myofibroblast. Many of the studies focused on mechanisms and factors that regulate induction of α-smooth muscle actin expression, a key and commonly used marker of the myofibroblast. These reveal complex and multifactorial mechanisms involving transcriptional and epigenetic regulation and implicating diverse cell-signaling pathways, including those activated by the potent fibrogenic cytokine transforming growth factor β. Despite these extensive studies, many aspects remain poorly understood, with the suggestion that additional novel mechanisms remain to be discovered. Future studies with the help of newly developed technical advancements should expedite discovery in this direction.
组织损伤会引发修复反应，其中一个关键的间充质成分提供了必要的结缔组织，用于随后的再生或病理性纤维化。成纤维细胞是涉及这种结缔组织反应的主要间充质细胞类型，它以激活或分化的形式参与修复过程。肌成纤维细胞代表这种激活的间充质细胞，是细胞外基质和炎症/纤维化细胞因子的主要来源，并参与伤口收缩。尽管成功的愈合导致肌成纤维细胞逐渐消失，但它们的持续存在与慢性和进行性纤维化有关。因此，阐明肌成纤维细胞发生的机制应该为慢性纤维化疾病的发病机制以及它们的管理和控制的治疗策略提供深入的了解。虽然成纤维细胞是肌成纤维细胞的一个有据可查的祖细胞，但最近的研究表明，还有其他潜在的前体细胞有可能产生肌成纤维细胞。许多研究集中在调节α-平滑肌肌动蛋白表达诱导的机制和因素上，α-平滑肌肌动蛋白是肌成纤维细胞的一个关键且常用的标志物。这些发现揭示了涉及转录和表观遗传调控的复杂和多因素机制，并涉及多种细胞信号通路，包括由强效纤维生成细胞因子转化生长因子β激活的信号通路。尽管进行了这些广泛的研究，但许多方面仍未得到很好的理解，有迹象表明，还需要发现其他新的机制。在新开发的技术进步的帮助下，未来的研究应该会加速这一方向的发现。
