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微小RNA-21/PTEN轴通过增强树突状细胞促进皮肤伤口愈合。

MiR-21/PTEN Axis Promotes Skin Wound Healing by Dendritic Cells Enhancement.

作者信息

Han Zhaofeng, Chen Ya, Zhang Yile, Wei Aizhou, Zhou Jian, Li Qian, Guo Lili

机构信息

Department of Burn and Reconstruction, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450002, China.

Reproductive Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450002, China.

出版信息

J Cell Biochem. 2017 Oct;118(10):3511-3519. doi: 10.1002/jcb.26026. Epub 2017 May 18.

DOI:10.1002/jcb.26026
PMID:28374893
Abstract

A number of miRNAs associated with wound repair have been identified and characterized, but the mechanism has not been fully clarified. MiR-21 is one of wound-related lncRNAs, and the study aimed to explore the functional involvement of miR-21 and its concrete mechanism in wound healing. In this study, the rat model of skin wounds was established. The expression of miR-21, PTEN and related molecules of wound tissues or cells was determined by quantitative real-time PCR and Western blot, respectively. The regulatory role of miR-21 on PTEN was examined by luciferase reporter gene assay. Flow cytometry assay was applied to measure cell number changes. MiR-21 was upregulated at 6, 24, 48, 72 h after model establishment, and the increase reached a maximum at 24 h in wound tissues. MMP-9 expression presented the same tread as miR-21 and was significantly enhanced within 6 h of wound formation, and then remained to be increased to the maximum at 24 h. The increase of miR-21 was accompanied by the increase of cell total number and DCs ratio in wound fluids. MiR-21 overexpression significantly improved the healing of skin wounds and increased the ratio of DCs in rats. The results of using FL confirmed that miR-21 overexpression obviously promoted DCs differentiation. Additionally, miR-21 could activate AKT/PI3K signaling pathway via inhibition of PTEN. MiR-21 contributes to wound healing via inhibition of PTEN that activated AKT/PI3K signaling pathway to increase DCs. J. Cell. Biochem. 118: 3511-3519, 2017. © 2017 Wiley Periodicals, Inc.

摘要

一些与伤口修复相关的微小RNA(miRNA)已被鉴定和表征,但其机制尚未完全阐明。MiR-21是与伤口相关的长链非编码RNA之一,本研究旨在探讨MiR-21在伤口愈合中的功能作用及其具体机制。在本研究中,建立了大鼠皮肤伤口模型。分别通过定量实时PCR和蛋白质免疫印迹法测定伤口组织或细胞中MiR-21、PTEN及相关分子的表达。通过荧光素酶报告基因检测法检测MiR-21对PTEN的调控作用。应用流式细胞术检测细胞数量变化。模型建立后6、24、48、72小时,伤口组织中MiR-21表达上调,在24小时时增加至最高。基质金属蛋白酶-9(MMP-9)表达与MiR-21呈相同趋势,在伤口形成后6小时内显著增强,然后在2小时时继续增加至最高。MiR-21的增加伴随着伤口液中细胞总数和树突状细胞(DCs)比例的增加。MiR-21过表达显著促进了大鼠皮肤伤口的愈合并增加了DCs比例。荧光素酶报告基因检测结果证实MiR-21过表达明显促进了DCs分化。此外,MiR-21可通过抑制PTEN激活AKT/PI3K信号通路。MiR-21通过抑制PTEN激活AKT/PI3K信号通路增加DCs从而促进伤口愈合。《细胞生物化学杂志》118: 3511 - 3519, 2017。© 2017威利期刊公司。

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