MiR‐488‐3p facilitates wound healing through CYP1B1‐mediated Wnt/β‐catenin signaling pathway by targeting MeCP2

Abstract

ABSTRACTIntroductionDiabetic wounds are difficult to heal, but the pathogenesis is unknown. MicroRNAs (miRNAs) are thought to play important roles in wound healing. The effect of miR‐488‐3p in wound healing was studied in this article.Materials and MethodsThe gene methylation was measured by methylation specific PCR (MSP) assay. A dual‐luciferase reporter assay was adopted to analyze the interaction between miR‐488‐3p and MeCP2.ResultsCytochrome P450 1B1 (CYP1B1) is a monooxygenase belonging to the cytochrome P450 family that aids in wound healing. Our findings showed that the miR‐488‐3p and CYP1B1 expression levels were much lower in wound tissues of diabetics with skin defects, but the methyl‐CpG‐binding protein 2 (MeCP2) level was significantly higher than that in control skin tissues. MiR‐488‐3p overexpression increased cell proliferation and migration, as well as HUVEC angiogenesis, while inhibiting apoptosis, according to function experiments. In vitro, MeCP2 inhibited wound healing by acting as a target of miR‐488‐3p. We later discovered that MeCP2 inhibited CYP1B1 expression by enhancing its methylation state. In addition, CYP1B1 knockdown inhibited wound healing. Furthermore, MeCP2 overexpression abolished the promoting effect of miR‐488‐3p on wound healing. It also turned out that CYP1B1 promoted wound healing by activating the Wnt4/β‐catenin pathway. Animal experiments also showed that miR‐488‐3p overexpression could accelerate wound healing in diabetic male SD rats.ConclusionsMiR‐488‐3p is a potential therapeutic target for diabetic wound healing since it improved wound healing by activating the CYP1B1‐mediated Wnt4/‐catenin signaling cascade via MeCP2.