RUNX2 promotes vascular injury repair by activating miR-23a and inhibiting TGFBR2

Abstract

Background: Previous evidence has suggested that the transcription factor, runt-related transcription factor 2 (RUNX2), promotes the repair of vascular injury and activates the expression of microRNA-23a (miR-23a). TGF-β receptor type II (TGFBR2) has been found to mediate smooth muscle cells (SMCs) following arterial injury. However, the interactions among RUNX2, miR-23a and TGFBR2 in vascular injury have not been investigated thoroughly yet. Therefore, we aim to explore the mechanism of how RUNX2 triggers the expression of miR-23a and its effects on the repair of vascular injury.Methods: C57BL/6 mice were used to produce a model of arterial injury in vivo. Mouse arterial SMCs were isolated for in vitro cell injury induction by 100 nmol/L tumor necrosis factor-α (TNF-α). Gain-and lossof-function studies were conducted to assess cell viability and apoptosis by using cell counting kit (CCK)-8 assay and flow cytometry respectively. The levels of TNF-α, interleukin-6 (IL-6), and monocyte chemotactic protein-1 (MCP-1) were examined by enzyme-linked immunosorbent assay (ELISA). The interaction between RUNX2 and miR-23a was identified by chromatin immunoprecipitation (ChIP) and dual luciferase reporter assays, while the targeting relationship between miR-23a and TGFBR2 was analyzed by RNA immunoprecipitation (RIP) and dual luciferase reporter assays.Results: Both RUNX2 and miR-23a exhibited low levels of expressions, while TGFBR2 had a high level of expression in mice with induced arterial injury. RUNX2 was found to bind to the promoter of miR-23a and activate miR-23a, while miR-23a targeted TGFBR2. Ectopic RUNX2 expression inhibited inflammatory cell infiltration, and promoted collagen content by upregulating miR-23a and downregulating TGFBR2. Furthermore, the overexpression of RUNX2 increased viability and decreased apoptosis in vascular smooth muscle cells (VSMCs) by activating miR-23a. Conclusions:The overexpression of RUNX2 elevated the expression of miR-23, thus inhibiting TGFBR2 and promoting vascular injury repair.

LncRNA FTX ameliorates neuropathic pain by targeting miR-320a in a rat model of chronic constriction injury

“…It was also involved in nerve protrusion growth and migration after sciatic nerve compression [7]. RUNX2 is involved in the inflammatory response in a variety of diseases, such as cardiac aortic valve calcification [30], vascular injury repair [37], osteoarthritis [23], and atherosclerosis [4]. More importantly, the targeting relationship of RUNX2 with miR-320a was confirmed in polycystic soft nest syndrome [41], osteoarthritis [32], and MSC adipocyte differentiation [11].…”