DDR1-Akt signaling pathway in myocardial fibrosis of rats with hypertension / 西安交通大学学报(医学版)

ABSTRACT

Objective: To explore the role of collagen I-discoidin domain receptor 1 (DDR1)-protein kinase B (Akt) signaling pathway in the proliferation of myocardial fibroblasts (MFBs) of hypertensive rats. Methods:A hypertensive rat model via abdominal aorta constriction (AAC) was used in this study. We compared body weight, tail artery systolic blood pressure (SBP) and left ventricular mass index (LVMI) among blank, sham, AAC and spontaneously hypertensive rat (SHR) groups. Expression and phosphorylation levels of DDR1 and Akt were detected using immunoprecipitation in combination with Western blot. We analyzed the correlation between DDR1 phosphorylation level and SBP (or LVMI). Cell proliferation, expression and phosphorylation levels of DDR1 and Akt in primary MFBs of SHR rats were detected using BrdU labeling assay and Western blot, respectively. Results: There was no significant difference in body weight among the four groups (P>0.05). In AAC and SHR groups, SBP, LVMI and phosphorylation levels of DDR1 and Akt were significantly increased. Both SBP and LVMI were positively correlated with phosphorylation level of DDR1. In vitro, collagen I accelerated cell proliferation and promoted DDR1 and Akt phosphorylation in MFBs. Conclusion: This research suggests that an activated collagen -DDR1-Akt pathway exists during the myocardial fibrosis process of rats with hypertension. DDR1 inhibitors may have the potential to relieve myocardial fibrosis.