Zent Joshua, Guo Lian-Wang
Medical Scientist Training Program, the Ohio State University, Columbus, Columbus, Ohio, USA.
Department of Surgery, Department of Physiology & Cell Biology, College of Medicine, Davis Heart and Lung Research Institute, Wexner Medical Center, the Ohio State University, Columbus, Ohio, USA.
Cell Physiol Biochem. 2018;49(3):848-868. doi: 10.1159/000493217. Epub 2018 Sep 5.
Myofibroblasts are central mediators of fibrosis. Typically derived from resident fibroblasts, myofibroblasts represent a heterogeneous population of cells that are principally defined by acquired contractile function and high synthetic ability to produce extracellular matrix (ECM). Current literature sheds new light on the critical role of ECM signaling coupled with mechanotransduction in driving myofibroblastic activation. In particular, transforming growth factor β1 (TGF-β1) and extra domain A containing fibronectin (EDA-FN) are thought to be the primary ECM signaling mediators that form and also induce positive feedback loops. The outside-in and inside-out signaling circuits are transmitted and integrated by TGF-β receptors and integrins at the cell membrane, ultimately perpetuating the abundance and activities of TGF-β1 and EDA-FN in the ECM. In this review, we highlight these conceptual advances in understanding myofibroblastic activation, in hope of revealing its therapeutic anti-fibrotic implications.
肌成纤维细胞是纤维化的核心介质。肌成纤维细胞通常源自驻留的成纤维细胞，代表一类异质性细胞群体，其主要特征是具有获得性收缩功能和产生细胞外基质（ECM）的高合成能力。当前的文献为ECM信号传导与机械转导在驱动肌成纤维细胞活化中的关键作用提供了新的见解。特别是，转化生长因子β1（TGF-β1）和含额外结构域A的纤连蛋白（EDA-FN）被认为是形成并诱导正反馈回路的主要ECM信号介质。胞外到胞内和胞内到胞外的信号通路通过细胞膜上的TGF-β受体和整合素进行传递和整合，最终使ECM中TGF-β1和EDA-FN的丰度和活性持续存在。在本综述中，我们重点介绍了在理解肌成纤维细胞活化方面的这些概念进展，希望揭示其抗纤维化治疗意义。
