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Zhiyong Yang, Xinzhong Zhang, Naipeng Guo, Bin Li, Sheng Zhao
(Department of Cardiology, Shengjing Hospital Affiliated to China Medical University, Shenyang, Liaoning, China (mainland))
Med Sci Monit 2016; 22:4937-4946
The aim of this study was to explore the regulating effects of Substance P (SP) on the collagen synthesis of rat myocardial fibroblasts (CFBs) induced by angiotensin II (Ang II) and its potential mechanism.
MATERIAL AND METHODS: The CFBs of a neonatal SD rat were separately cultured and divided into the control group, Ang II treatment group, and treatment groups with different concentrations of SP, Ang II +; each group was given corresponding treatment respectively.
RESULTS: Ang II successfully induced the collagen synthesis of CFBs. Compared with the control group, the phosphorylation levels of TGF-β, erk, and smad2/3 were higher (p<0.05). Different concentrations of SP had an effect on Ang II-induced CFBs, reduced the collagen synthesis of CFBs, and increased the expressions of SP receptors, accompanied by lowering TGF-β protein, erk protein phosphorylation level, and smad2/3 protein phosphorylation level (p<0.05). Moreover, the higher the concentrations of SP, the more obvious of an effect it exerted. Treating the Ang II + SP group with aprepitant reduced the inhibiting effects of SP on collagen synthesis. The expression changes of collagen I and collagen III detected by immunocytochemistry were exactly in accordance with the results of qPCR and Western blotting.
CONCLUSIONS: SP can inhibit collagen synthesis of CFBs after Ang II inducing which may adjust the downstream signaling pathways associated protein including TGF-β, erk and smad2/3. SP can block the progress of myocardial fibrosis and is dose dependent, which is expected to be a promising target for the treatment of myocardial fibrosis.