title: Substance P Inhibits the Collagen Synthesis of Rat Myocardial Fibroblasts Induced by Ang II.
abstract: 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.
authors.affiliation: Department of Cardiology, Shengjing Hospital Affiliated to China Medical University, Shenyang, Liaoning, China (mainland).
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Shengjing Hospital Affiliated to China Medical University, Shenyang, Liaoning, China (mainland).
authors.forename: Xinzhong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Shengjing Hospital Affiliated to China Medical University, Shenyang, Liaoning, China (mainland).
authors.forename: Naipeng
authors.initials: N
authors.lastname: Guo
authors.affiliation: Department of Cardiology, Shengjing Hospital Affiliated to China Medical University, Shenyang, Liaoning, China (mainland).
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Cardiology, Capital Medical University Electric Power Teaching Hospital, Beijing, China (mainland).
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhao
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005355:Fibrosis; D006321:Heart / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D013373:Substance P / Q000378:metabolism / Q000494:pharmacology*; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D051899:Smad2 Protein; C497784:Smad2 protein, rat; D051900:Smad3 Protein; C497787:Smad3 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000804:Angiotensin II; D013373:Substance P; D003094:Collagen