title: Curcumin suppresses transforming growth factor-β1-induced cardiac fibroblast differentiation via inhibition of Smad-2 and p38 MAPK signaling pathways.
abstract: The differentiation of cardiac fibroblasts (CFs) into myofibroblasts and the subsequent deposition of the extracellular matrix is associated with myocardial fibrosis following various types of myocardial injury. In the present study, the effect of curcumin, which is a pharmacologically-safe natural compound from theCurcuma longaherb, on transforming growth factor (TGF)-β1-induced CFs was investigated, and the underlying molecular mechanisms were examined. The expression levels of α-smooth muscle actin (SMA) stress fibers were investigated using western blotting and immunofluorescence in cultured neonatal rat CFs. Protein and mRNA expression levels of α-SMA and collagen type I (ColI) were determined by western blotting and reverse transcription-quantitative polymerase chain reaction. In addition, the activation of Smad2 and p38 was examined using western blotting. Curcumin, SB431542 (a TGF-βR-Smad2 inhibitor) and SB203580 (a p38 inhibitor) were used to inhibit the stimulation by TGF-β1. The results demonstrated that the TGF-β1-induced expression of α-SMA and ColI was suppressed by curcumin at the mRNA and protein levels, while SB431542 and SB203580 induced similar effects. Furthermore, phosphorylated Smad-2 and p38 were upregulated in TGF-β1-induced CFs, and these effects were substantially inhibited by curcumin administration. In conclusion, the results of the present study demonstrated that treatment with curcumin effectively suppresses TGF-β1-induced CF differentiation via Smad-2 and p38 signaling pathways. Thus, curcumin may be a potential therapeutic agent for the treatment of cardiac fibrosis.
authors.affiliation: Department of Cardiac Surgery, Shanxi Cardiovascular Hospital, Taiyuan, Shanxi 030024, P.R. China.
authors.forename: Huzi
authors.initials: H
authors.lastname: Liu
authors.affiliation: Pediatric Heart Center, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, P.R. China.
authors.forename: Aijun
authors.initials: A
authors.lastname: Liu
authors.affiliation: Outpatient Department, Shanxi Cardiovascular Hospital, Taiyuan, Shanxi 030024, P.R. China.
authors.forename: Chunli
authors.initials: C
authors.lastname: Shi
authors.affiliation: Department of Cardiology, Shanxi Cardiovascular Hospital, Taiyuan, Shanxi 030024, P.R. China.
authors.forename: Bao
authors.initials: B
authors.lastname: Li
keywords: Smad2; cardiac fibroblast; curcumin; p38 mitogen-activated protein kinase; transforming growth factor-β1