Chun Wang, Li Huang, Juan Li, Dan Liu, Biaoliang Wu
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引用次数: 0
Abstract
Diabetic foot ulcer (DFU) is one major, common and serious chronic complication of diabetes mellitus, which is characterized by high incidence, high risk, high burden, and high treatment difficulty and is a leading cause of disability and death in patients with diabetes. Long-term hyperglycemia can result in cellular dysfunction of fibroblasts, which play pivotal roles in wound healing. MicroRNAs (miRNAs) were reported to mediate the pathological processes of multiple diseases, including diabetic wound healing. This research aimed to investigate the functional role of miR-145-5p in high-glucose (HG)-exposed fibroblasts and in DFU mouse models. Human foreskin fibroblast cells (HFF-1) were stimulated by HG to induce cell injury. MiR-145-5p level in HG-stimulated HFF-1 cells was detected via RT-qPCR. The binding between miR-145-5p and PDGFD was validated by Luciferase reporter assay. The effects of the miR-145-5p/PDGFD axis on the viability, migration, and apoptosis of HG-exposed HFF-1 cells were determined by CCK-8, wound healing, and flow cytometry assays. DFU mouse models were subcutaneously injected at the wound edges with miR-145-5p inhibitor/mimics. Images of the wounds were captured on day 0 and 8 post-injection, and wound samples were collected after mice were sacrificed for histological analysis by H&E staining. HG decreased cell viability and increased miR-145-5p expression in HFF-1 cells in a dose- and time-dependent manner. MiR-145-5p downregulation promoted cell viability and migration and inhibited cell apoptosis of HG-stimulated HFF-1 cells, while miR-145-5p overexpression exerted an opposite effect on cell viability, migration, and apoptosis. PDGFD was a direct target gene of miR-145-5p, whose silencing reversed the influence of miR-145-5p downregulation on HG-induced cellular dysfunction of HFF-1 cells. Additionally, downregulating miR-145-5p facilitated while overexpressing miR-145-5p inhibited wound healing in DFU mouse models. MiR-145-5p level was negatively associated with PDGFD level in wound tissue samples of DFU mouse models. MiR-145-5p inhibition improves wound healing in DFU through upregulating PDGFD expression.
期刊介绍:
Biochemical Genetics welcomes original manuscripts that address and test clear scientific hypotheses, are directed to a broad scientific audience, and clearly contribute to the advancement of the field through the use of sound sampling or experimental design, reliable analytical methodologies and robust statistical analyses.
Although studies focusing on particular regions and target organisms are welcome, it is not the journal’s goal to publish essentially descriptive studies that provide results with narrow applicability, or are based on very small samples or pseudoreplication.
Rather, Biochemical Genetics welcomes review articles that go beyond summarizing previous publications and create added value through the systematic analysis and critique of the current state of knowledge or by conducting meta-analyses.
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