Scimago Lab
powered by Scopus
eISSN: 2325-4416
call: +1.631.470.9640
Mon-Fri 10 am - 2 pm EST




Substance P Inhibits the Collagen Synthesis of Rat Myocardial Fibroblasts Induced by Ang II

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

DOI: 10.12659/MSM.898454

Available online:

Published: 2016-12-16

BACKGROUND: 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.

Keywords: Animals, Angiotensin II - pharmacology, Cells, Cultured, Collagen - biosynthesis, Collagen Type I - metabolism, Collagen Type III - metabolism, Fibroblasts - metabolism, Fibrosis, Heart - drug effects, Myocardium - pathology, Rats, Rats, Sprague-Dawley, Signal Transduction - drug effects, Smad2 Protein - metabolism, Smad3 Protein - metabolism, Substance P - pharmacology, Transforming Growth Factor beta, Transforming Growth Factor beta1 - metabolism