BACKGROUND Shifting from the inflammatory to the proliferative phase represents a pivotal step during managing diabetic foot ulcers(DFUs);however,existing medical interventions remain insufficient.MicroRNAs(miRs)highl...BACKGROUND Shifting from the inflammatory to the proliferative phase represents a pivotal step during managing diabetic foot ulcers(DFUs);however,existing medical interventions remain insufficient.MicroRNAs(miRs)highlight notable capacity for accelerating the repair process of DFUs.Previous research has demonstrated which miR-122-5p regulates matrix metalloproteinases under diabetic conditions,thereby influencing extracellular matrix dynamics.AIM To investigate the impact of miR-122-5p on the transition from the inflammatory to the proliferative stage in DFU.METHODS Analysis for miR-122-5p expression in skin tissues from diabetic ulcer patients and mice was analyzed using quantitative real-time polymerase chain reaction(qRT-PCR).A diabetic wound healing model induced by streptozotocin was used,with mice receiving intradermal injections of adeno-associated virus-DJ encoding empty vector or miR-122.Skin tissues were retrieved at 3,7,and 14 days after injury for gene expression analysis,histology,immunohistochemistry,and network studies.The study explored miR-122-5p’s role in macrophage-fibroblast interactions and its effect on transitioning from inflammation to proliferation in DFU healing.RESULTS High-throughput sequencing revealed miR-122-5p as crucial for DFU healing.qRT-PCR showed significant upregulation of miR-122-5p within diabetic skin among DFU individuals and mice.Western blot,along with immunohistochemical and enzyme-linked immunosorbent assay,demonstrating the upregulation of inflammatory mediators(hypoxia inducible factor-1α,matrix metalloproteinase 9,tumor necrosis factor-α)and reduced fibrosis markers(fibronectin 1,α-smooth muscle actin)by targeting vascular endothelial growth factor.Fluorescence in situ hybridization indicated its expression localized to epidermal keratinocytes and fibroblasts in diabetic mice.Immunofluorescence revealed enhanced increased presence of M1 macrophages and reduced M2 polarization,highlighting its role in inflammation.MiR-122-5p elevated inflammatory cytokine levels while suppressing fibrotic activity from fibroblasts exposed to macrophage-derived media,highlighting its pivotal role in regulating DFU healing.CONCLUSION MiR-122-5p impedes cutaneous healing of diabetic mice via enhancing inflammation and inhibiting fibrosis,offering insights into miR roles in human skin wound repair.展开更多
乙型肝炎病毒(hepatitis B virus,HBV)与宿主肝细胞存在复杂的相互作用并与病毒复制及相关慢性肝病、肝硬化、肝癌的发生\发展有关。microRNA(miRNA)-122是肝脏含量最多的特异性miRNA,大量研究揭示了其在肝细胞脂质代谢、增殖、生物钟...乙型肝炎病毒(hepatitis B virus,HBV)与宿主肝细胞存在复杂的相互作用并与病毒复制及相关慢性肝病、肝硬化、肝癌的发生\发展有关。microRNA(miRNA)-122是肝脏含量最多的特异性miRNA,大量研究揭示了其在肝细胞脂质代谢、增殖、生物钟调节及丙型肝炎病毒感染过程中的重要性。近几年的研究发现肝细胞miRNA-122与HBV复制及HBV的致病机制存在密切关联,并与乙肝肝硬化及肝癌的发生及预后相关,基于miRNA-122的诊断及治疗方法的探索也取得了一定的进展。本文综述了miRNA-122与乙型肝炎病毒复制及相关疾病进展的研究现状。展开更多
基金Supported by the National Natural Science Foundation of China,No.82274528.
文摘BACKGROUND Shifting from the inflammatory to the proliferative phase represents a pivotal step during managing diabetic foot ulcers(DFUs);however,existing medical interventions remain insufficient.MicroRNAs(miRs)highlight notable capacity for accelerating the repair process of DFUs.Previous research has demonstrated which miR-122-5p regulates matrix metalloproteinases under diabetic conditions,thereby influencing extracellular matrix dynamics.AIM To investigate the impact of miR-122-5p on the transition from the inflammatory to the proliferative stage in DFU.METHODS Analysis for miR-122-5p expression in skin tissues from diabetic ulcer patients and mice was analyzed using quantitative real-time polymerase chain reaction(qRT-PCR).A diabetic wound healing model induced by streptozotocin was used,with mice receiving intradermal injections of adeno-associated virus-DJ encoding empty vector or miR-122.Skin tissues were retrieved at 3,7,and 14 days after injury for gene expression analysis,histology,immunohistochemistry,and network studies.The study explored miR-122-5p’s role in macrophage-fibroblast interactions and its effect on transitioning from inflammation to proliferation in DFU healing.RESULTS High-throughput sequencing revealed miR-122-5p as crucial for DFU healing.qRT-PCR showed significant upregulation of miR-122-5p within diabetic skin among DFU individuals and mice.Western blot,along with immunohistochemical and enzyme-linked immunosorbent assay,demonstrating the upregulation of inflammatory mediators(hypoxia inducible factor-1α,matrix metalloproteinase 9,tumor necrosis factor-α)and reduced fibrosis markers(fibronectin 1,α-smooth muscle actin)by targeting vascular endothelial growth factor.Fluorescence in situ hybridization indicated its expression localized to epidermal keratinocytes and fibroblasts in diabetic mice.Immunofluorescence revealed enhanced increased presence of M1 macrophages and reduced M2 polarization,highlighting its role in inflammation.MiR-122-5p elevated inflammatory cytokine levels while suppressing fibrotic activity from fibroblasts exposed to macrophage-derived media,highlighting its pivotal role in regulating DFU healing.CONCLUSION MiR-122-5p impedes cutaneous healing of diabetic mice via enhancing inflammation and inhibiting fibrosis,offering insights into miR roles in human skin wound repair.
文摘乙型肝炎病毒(hepatitis B virus,HBV)与宿主肝细胞存在复杂的相互作用并与病毒复制及相关慢性肝病、肝硬化、肝癌的发生\发展有关。microRNA(miRNA)-122是肝脏含量最多的特异性miRNA,大量研究揭示了其在肝细胞脂质代谢、增殖、生物钟调节及丙型肝炎病毒感染过程中的重要性。近几年的研究发现肝细胞miRNA-122与HBV复制及HBV的致病机制存在密切关联,并与乙肝肝硬化及肝癌的发生及预后相关,基于miRNA-122的诊断及治疗方法的探索也取得了一定的进展。本文综述了miRNA-122与乙型肝炎病毒复制及相关疾病进展的研究现状。
