Department of Nephrology & Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangdong Provincial Hospital of Chinese Medicine, Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China.
Department of Medicine & Therapeutics, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China.
Future Med Chem. 2020 May;12(9):853-866. doi: 10.4155/fmc-2020-0005. Epub 2020 Apr 1.
Renal fibrosis is a hallmark of chronic kidney disease. Although considerable achievements in the pathogenesis of renal fibrosis have been made, the underlying mechanisms of renal fibrosis remain largely to be explored. Now we have reached the consensus that TGF-β is a master regulator of renal fibrosis. Indeed, TGF-β regulates renal fibrosis via both canonical and noncanonical TGF-β signaling. Moreover, ongoing renal inflammation promotes fibrosis as inflammatory cells such as macrophages, conventional T cells and mucosal-associated invariant T cells may directly or indirectly contribute to renal fibrosis, which is also tightly regulated by TGF-β. However, anti-TGF-β treatment for renal fibrosis remains ineffective and nonspecific. Thus, research into mechanisms and treatment of renal fibrosis remains highly challenging.
肾纤维化是慢性肾脏病的一个标志。尽管在肾纤维化发病机制方面已经取得了相当大的成就,但肾纤维化的潜在机制仍在很大程度上有待探索。现在我们已经达成共识,即 TGF-β 是肾纤维化的主要调节因子。事实上,TGF-β 通过经典和非经典 TGF-β 信号通路来调节肾纤维化。此外,持续的肾脏炎症促进纤维化,因为诸如巨噬细胞、常规 T 细胞和黏膜相关不变 T 细胞等炎症细胞可能直接或间接地导致肾纤维化,而 TGF-β 也对其进行了严格的调控。然而,抗 TGF-β 治疗肾纤维化仍然无效且没有特异性。因此,研究肾纤维化的机制和治疗方法仍然极具挑战性。