MicroRNA-210–5p alleviates cardiac fibrosis via targeting transforming growth factor-beta type I receptor in rats on high sodium chloride (NaCl)-based diet

Abstract

The present study was designed to explore whether high sodium chloride (NaCl)-based diet (HSD) caused cardiac fibrosis regardless of blood pressure in Sprague-Dawley (SD) rats, and to further determine the effects and the underlying mechanisms of microRNA (miR)-210–5p on HSD-induced cardiac fibrosis in rats or NaCl-induced cardiac fibroblast activation in neonatal rat cardiac fibroblasts (NRCFs). The SD rats received 8% HSD, and NRCFs were treated with NaCl. The levels of collagen I, alpha-smooth muscle actin (α-SMA) and transforming growth factor-beta 1 (TGF-β1) were increased in the heart of hypertension (HTN), hypertension-prone (HP) and hypertension-resistant (HR) rats on HSD in vivo. NaCl increased the levels of collagen I, α-SMA and TGF-β1 in NRCFs in vitro. The level of miR-210–5p was reduced in both NBD-induced rats’ hearts and NaCl-treated NRCFs, which was consistent with the results of miR high-throughput sequencing in NRCFs. The HSD or NaCl-induced increases of collagen I, α-SMA and TGF-β1 were inhibited by miR-210–5p agomiR in vitro and in vivo, respectively. miR-210–5p antagomiR could mimic the pathological effects of NaCl in NRCFS. Bioinformatics analysis and luciferase reporter assays demonstrated that TGF-β type I receptor (TGFBR1) was a direct target gene of miR-210–5p. These results indicated that HSD resulted in cardiac fibrosis regardless of blood pressure. The upregulation of miR-210–5p could attenuate cardiac fibroblast activation in NRCFS via targeting TGFBR1. Thus, upregulating miR-210–5p might be a strategy for the treatment of cardiac fibrosis.