Cellular and molecular mechanisms in fibrosis
Cellular and molecular mechanisms in fibrosis
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DOI：
10.1111/exd.14193
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发表时间：
2020-10-09
影响因子：
3.6
通讯作者：
Distler, Joerg H. W.
中科院分区：
文献类型：
--
作者：
Dees, Clara;Chakraborty, Debomita;Distler, Joerg H. W.
成纤维细胞的激活是伤口愈合等生理性组织重建所必需的。然而，当调控机制被破坏，成纤维细胞持续激活时，细胞外基质蛋白的进行性沉积会导致组织纤维化，从而导致受影响器官的功能障碍甚至丧失功能。虽然纤维化已被认为是现代社会发病率和死亡率的主要原因，但可用于直接干扰成纤维细胞释放细胞外基质的治疗方案很少。然而，近年来的密集研究发现，有几条途径是核心纤维化机制，它们在不同的纤维化疾病和器官中共享。我们在这里讨论那些核心通路的选择，特别是促纤维化的转化生长因子-β通路的下游，这些通路是可用药的，可以从试验台转移到床边。
The activation of fibroblasts is required for physiological tissue remodelling such as wound healing. However, when the regulatory mechanisms are disrupted and fibroblasts remain persistently activated, the progressive deposition of extracellular matrix proteins leads to tissue fibrosis, which results in dysfunction or even loss of function of the affected organ. Although fibrosis has been recognized as a major cause of morbidity and mortality in modern societies, there are only few treatment options available that directly disrupt the release of extracellular matrix from fibroblasts. Intensive research in recent years, however, identified several pathways as core fibrotic mechanisms that are shared across different fibrotic diseases and organs. We discuss herein selection of those core pathways, especially downstream of the profibrotic TGF-beta pathway, which are druggable and which may be transferable from bench to bedside.