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抑制 miR-618 促进角质形成细胞增殖和迁移，增强小鼠的伤口愈合。

Inhibiting miR-618 Promotes Keratinocytes Proliferation and Migration to Enhance Wound Healing in Mice.

机构信息

School of Life Sciences, Shanghai University, Shanghai 200444, China.

School of Medicine, Shanghai University, Shanghai 200444, China.

出版信息

Int J Mol Sci. 2024 Jul 11;25(14):7617. doi: 10.3390/ijms25147617.

DOI:10.3390/ijms25147617
PMID:39062857
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11277496/
Abstract

The delay in wound healing caused by chronic wounds or pathological scars is a pressing issue in clinical practice, imposing significant economic and psychological burdens on patients. In particular, with the aging of the population and the increasing incidence of diseases such as diabetes, impaired wound healing is one of the growing health problems. MicroRNA (miRNA) plays a crucial role in wound healing and regulates various biological processes. Our results show that miR-618 was significantly upregulated during the inflammatory phase of wound healing.Subsequently, miR-618 promotes the secretion of pro-inflammatory cytokines and regulates the proliferation and migration of keratinocytes. Mechanistically, miR-618 binds to the target gene- and inhibits the PI3K-Akt signaling pathway, inhibiting the epithelial-mesenchymal transition (EMT) of keratinocytes. In addition, the PI3K-Akt signaling pathway induces the enrichment of nuclear miR-618, and miR-618 binds to the promoter of to regulate gene transcription. Intradermal injection of miR-618 antagomir around full-thickness wounds in peridermal mice effectively accelerates wound closure compared to control. In conclusion, miR-618 antagomir can be a potential therapeutic agent for wound healing.

摘要

慢性伤口或病理性瘢痕导致的伤口愈合延迟是临床实践中的一个紧迫问题，给患者带来了巨大的经济和心理负担。特别是随着人口老龄化和糖尿病等疾病发病率的增加，伤口愈合受损是日益严重的健康问题之一。微小 RNA（miRNA）在伤口愈合中起着至关重要的作用，调节着各种生物过程。我们的研究结果表明，miR-618 在伤口愈合的炎症期显著上调。随后，miR-618 促进促炎细胞因子的分泌，并调节角质形成细胞的增殖和迁移。在机制上，miR-618 与靶基因结合并抑制 PI3K-Akt 信号通路，抑制角质形成细胞的上皮-间充质转化（EMT）。此外，PI3K-Akt 信号通路诱导核 miR-618 的富集，miR-618 结合到 的启动子上调节基因转录。在全层伤口周围的真皮小鼠皮内注射 miR-618 拮抗剂，与对照组相比，能有效加速伤口闭合。总之，miR-618 拮抗剂可能成为伤口愈合的一种潜在治疗药物。

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