Gerarduzzi Casimiro, Di Battista John A
Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Institutes of Medicine, Rm 510, 77 Louis Pasteur Avenue, Boston, MA, 02115, USA.
Department of Medicine and Experimental Medicine, McGill University and the Division of Rheumatology, Royal Victoria Hospital, McGill University Health Centre Research Institute, 1001 Decarie Boul., Montréal, QC, H4A 3J1, Canada.
Inflamm Res. 2017 Jun;66(6):451-465. doi: 10.1007/s00011-016-1019-x. Epub 2016 Dec 31.
Fibrosis is a complex chronic disease characterized by a persistent repair response. Its pathogenesis is poorly understood but it is typically the result of chronic inflammation and maintained with the required activity of transforming growth factor-β (TGFβ) and extracellular matrix (ECM) tension, both of which drive fibroblasts to transition into a myofibroblast phenotype.
As the effector cells of repair, myofibroblasts migrate to the site of injury to deposit excessive amounts of matrix proteins and stimulate high levels of contraction. Myofibroblast activity is a decisive factor in whether a tissue is properly repaired by controlled wound healing or rendered fibrotic by deregulated repair. Extensive studies have documented the various contributing factors to an abrogated repair response. Though these fibrotic factors are known, very little is understood about the opposing antifibrotic molecules that assist in a successful repair, such as prostaglandin E2 (PGE) and ECM retraction. The following review will discuss the general development of fibrosis through the transformation of myofibroblasts, focusing primarily on the prominent profibrotic pathways of TGFβ and ECM tension and antifibrotic pathways of PGE and ECM retraction.
The idea is to understand the ways in which the cell, after an injury and inflammatory response, normally controls its repair mechanisms through its homeostatic regulators so as to mimic them therapeutically to control abnormal pathways.
纤维化是一种以持续修复反应为特征的复杂慢性疾病。其发病机制尚不清楚，但通常是慢性炎症的结果，并通过转化生长因子-β（TGFβ）的必要活性和细胞外基质（ECM）张力维持，这两者都会促使成纤维细胞转变为肌成纤维细胞表型。
作为修复的效应细胞，肌成纤维细胞迁移到损伤部位，沉积过量的基质蛋白并刺激高水平的收缩。肌成纤维细胞的活性是决定组织通过可控的伤口愈合进行正常修复还是因修复失调而纤维化的决定性因素。大量研究记录了导致修复反应受损的各种因素。尽管这些纤维化因子已为人所知，但对于有助于成功修复的相反抗纤维化分子，如前列腺素E2（PGE）和ECM回缩，人们了解甚少。以下综述将讨论通过肌成纤维细胞转化实现纤维化的一般过程，主要关注TGFβ和ECM张力的主要促纤维化途径以及PGE和ECM回缩的抗纤维化途径。
目的是了解细胞在损伤和炎症反应后，如何通过其稳态调节因子正常控制其修复机制，以便在治疗上模仿这些机制来控制异常途径。
