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.

Keywords: Bone morphogenetic protein 9; Fibroblast; Organ fibrosis; Signaling pathway.