Department of Pathophysiology, Basic Medical College of Nanchang University, Nanchang, 330006, PR China; Nanchang Joint Program, Queen Mary School, Nanchang University, Nanchang, China.
Department of Nuclear Medicine, Nanchang University Hospital, Nanchang, 330006, PR China.
Eur J Pharmacol. 2020 Sep 5;882:173291. doi: 10.1016/j.ejphar.2020.173291. Epub 2020 Jun 20.
Fibrosis is a common endpoint for chronic organic diseases. Many signaling pathways and cytokines are involved in the development of fibrosis. Recently, bone morphogenetic protein 9 (BMP9), a member of transforming growth factor-beta (TGF-β) superfamily, has been considered as a pivotal regulator in tissue fibrosis, and exerts its diverse effects on the activation of fibroblasts and the development of fibrotic diseases. BMP9 exhibits its functional roles largely through binding to type I BMP receptor activin receptor-like kinase 1 (ALK1), and then directly activates small mother against decapentaplegic (Smad) signaling which promotes or limits the expressions of pro-fibrotic genes. Accumulating studies have demonstrated that the aberrant BMP9/ALK1/Smad signaling pathway affects the fibrogenesis of various organs, but the exact role of BMP9 in fibrosis remains elusive and debatable. In the present review, reports from in vitro, in vivo and clinical studies regarding the functions and underlying mechanisms of the BMP9 signaling in tissue fibrosis, are widely summarized and discussed. In addition, the major components of the BMP9 signaling pathway and the potential interventions targeting this pathway are also described. This review will enrich our understanding of the BMP9 signaling pathway in organ fibrosis, and provide a novel clue for the potential interventions of organ fibrosis.
纤维化是慢性器质性疾病的共同终点。许多信号通路和细胞因子参与了纤维化的发展。最近，骨形态发生蛋白 9（BMP9），转化生长因子-β（TGF-β）超家族的成员，被认为是组织纤维化的关键调节因子，对成纤维细胞的激活和纤维化疾病的发展发挥着多样化的作用。BMP9 通过与 I 型 BMP 受体激活素受体样激酶 1（ALK1）结合来发挥其功能作用，然后直接激活小 Smad 信号通路，促进或限制促纤维化基因的表达。越来越多的研究表明，异常的 BMP9/ALK1/Smad 信号通路影响各种器官的纤维化，但 BMP9 在纤维化中的确切作用仍不清楚且存在争议。在本综述中，广泛总结和讨论了关于 BMP9 信号在组织纤维化中的功能和潜在机制的体外、体内和临床研究报告。此外，还描述了 BMP9 信号通路的主要组成部分和针对该通路的潜在干预措施。这篇综述将丰富我们对器官纤维化中 BMP9 信号通路的理解，并为器官纤维化的潜在干预提供新的线索。
