Article ; Online: MiR-488-3p facilitates wound healing through CYP1B1-mediated Wnt/β-catenin signaling pathway by targeting MeCP2.
Journal of diabetes investigation
2023 Volume 15, Issue 2, Page(s) 145–158
Abstract: Introduction: Diabetic 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 ... ...
Abstract | Introduction: Diabetic 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 methods: The 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. Results: Cytochrome 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. Conclusions: MiR-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. |
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MeSH term(s) | Animals ; Male ; Rats ; Cell Line, Tumor ; Cell Proliferation/genetics ; Cytochrome P-450 Enzyme System/metabolism ; Diabetes Mellitus ; Methyl-CpG-Binding Protein 2/metabolism ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Rats, Sprague-Dawley ; Wnt Signaling Pathway/genetics ; Wound Healing |
Chemical Substances | Cytochrome P-450 Enzyme System (9035-51-2) ; Methyl-CpG-Binding Protein 2 ; MicroRNAs ; Mecp2 protein, rat ; MIRN488 microRNA, rat ; Cyp1b1 protein, rat (EC 1.14.14.1) |
Language | English |
Publishing date | 2023-11-13 |
Publishing country | Japan |
Document type | Journal Article |
ZDB-ID | 2625840-7 |
ISSN | 2040-1124 ; 2040-1116 |
ISSN (online) | 2040-1124 |
ISSN | 2040-1116 |
DOI | 10.1111/jdi.14099 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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