Effects of miR-155 on hypertensive rats via regulating vascular mesangial hyperplasia

Vascular smooth muscle cell (VSMC) excessive proliferation is related to hypertension. The cell cycle inhibitory factor (p27) can arrest cell cycle, while its down-regulation is associated with hypertension. It is found that microRNA-155 (miR-155) plays a regulatory role in VSMC proliferation, while its relationship with hypertension is still unclear. Bioinformatics analysis reveals the targeted relationship between miR-155 and the 3'-UTR of p27 mRNA. This study aims to explore the role of miR-155 in regulating p27 expression, VSMC proliferation and apoptosis, and the pathogenesis of hypertension.

Dual luciferase reporter gene assay confirmed the relationship between miR-155 and p27. MiR-155, p27, α-smooth muscle actin (α-SMA), and Ki-67 expressions in the thoracic aorta media of rat hypertension model were detected. VSMCs were cultured in vitro and divided into five groups, including anti-miR-NC, anti-miR-155, pIRES2-blank, pIRES2-p27, and anti-miR-155 + pIRES2-p27 groups. Cell cycle was evaluated by using flow cytometry. Cell proliferation was detected with EdU staining. Hypertension rats were randomly divided into antagomir-155 and antagomir-control. Caudal artery systolic and diastolic pressures were measured.

MiR-155 targeted suppressed p27 expression. MiR-155 and Ki-67 expressions significantly enhanced, while p27 and α-SMA levels reduced in the tunica media from hypertension rats compared with control. Down-regulation of miR-155 and/or up-regulation of p27significantly declined cell proliferation and arrested cell cycle in G1 phase. Antagomir-155 injection markedly decreased systolic and diastolic pressures, elevated p27 and α-SMA expressions in media, and reduced the thickness of tunica media.

MiR-155 promoted VSMC proliferation by targeting p27. MiR-155 enhancement was related to hypertension. MiR-155 played a therapeutic effect on hypertension.