Chymase induces profibrotic response via transforming growth factor-β1/Smad activation in rat cardiac fibroblasts

摘要: Mast cell-derived chymase is implicated in myocardial fibrosis (MF), but the underlying mechanism of intracellular signaling remains unclear. Transforming growth factor-β1 (TGF-β1) identified as most important profibrotic cytokine, and Smad proteins are essential, not exclusive downstream components TGF-β1 signaling. Moreover, novel evidence indicates that there a cross talk between mitogen-activated protein kinase (MAPK) cascade. We investigated whether activated TGF-β1/Smad pathway its potential role MF by evaluating cardiac fibroblasts (CFs) proliferation collagen synthesis neonatal rats. MTT assay 3H-Proline incorporation revealed induced CFs dose-dependent manner. RT-PCR Western blot demonstrated only increased expression also upregulated phosphorylated-Smad2/3 protein. Furthermore, pretreatment with neutralizing antibody suppressed chymase-induced cell growth, production, activation. In contrast, blockade angiotensin II receptor had no effects on production action. Additionally, inhibition MAPK effect activation elicited chymase. These results suggest can promote via rather than II, which process MF.