Role of PDGFR-β/PI3K/AKT signaling pathway in PDGF-BB induced myocardial fibrosis in rats

American Journal of Translational Research

Zhe Yang¹  Lei Wang¹  Jiawei Wu¹  Likun Ma¹  Hai Fan¹  Bin Fan¹ 

关键词: Myocardial fibrosis;    myofibroblasts;    platelet-derived growth factor;    signaling pathway;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

Objective: To investigate the role of PDGFR-β/PI3K/AKT signaling pathway in the myocardial fibrosis. Methods: CFs were divided into following 4 groups: control group (CON), PDGF-BB group (P), PDGF-BB+IMA group (IMA), and PDGF-BB+LY294002 (LY). Results: Immunofluorescence staining showed about 90% of cells were positive for vimentin and 10% for α-SMA. After incubation for 7 days, fluorescence microscopy revealed more than 90% of cells were positive for α-SMA, which was significantly higher than that in CON group (P < 0.01), but markedly lower than that in IMA group and LY group (P < 0.01). The mRNA and protein expression of PDGFR-β, Col I, Col III, PI3K and Akt increased dramatically at 48 h after PDGF-BB treatment when compared with CON group (P < 0.01). However, IMA and LY294002 significantly inhibited the expression of PDGFR-β and p-PI3K (P < 0.05). In addition, the mRNA expression of PDGFR-β, PI3K and Akt in IMA group and LY group was also markedly lower than those in P group (P < 0.01), and the mRNA and protein expression of Col I and Col III reduced remarkably when compared with P group (P < 0.01). Of note, the mRNA expression of PDGFR-α was comparable among 4 groups, and PDGFR-β expression after PDGF-BB treatment increased significantly when compared with PDGFR-α expression (P < 0.01). Conclusion: PDGF-BB may induce CF proliferation and their transformation into myofibroblasts, which leads to increased synthesis of collagen, resulting in myocardial fibrosis. This is closely associated with PDGFR-β, but not PDGFR-α. PDGFR-β/PI3K/Akt signaling pathway is involved in the PDGF-BB induced myocardial fibrosis.

【 授权许可】

Unknown