FoxO1 mediates TGF-beta1-dependent cardiac myofibroblast differentiation.

摘要: Cardiac fibroblast differentiation to myofibroblast is a crucial process in the development of cardiac fibrosis and tightly dependent on transforming growth factor beta-1 (TGF-β1). The transcription forkhead box O1 (FoxO1) regulates many cell functions, including death by apoptosis, proliferation, differentiation. However, several aspects this remain unclear, role FoxO1 regulation TGF-β1. Here, we report that TGF-β1 stimulates expression, promoting its dephosphorylation, nuclear localization transcriptional activity cultured fibroblasts. also increases markers such as α-smooth muscle actin, connective tissue factor, pro-collagen I, whereas it decreases proliferation triggered fetal bovine serum. levels p21waf/cip-cycle inhibiting protein, cytostatic cycle arrest In addition, contractile capacity assessed collagen gel contraction assay. effect was prevented down-regulation enhanced overexpression. Thus, our findings reveal regulated plays critical We propose an attractive new target for anti-fibrotic therapy.