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微小RNA-222通过基质金属蛋白酶1调节增生性瘢痕中成纤维细胞的活力。

MicroRNA-222 regulates the viability of fibroblasts in hypertrophic scars via matrix metalloproteinase 1.

作者信息

Zhang Yi, Lin Xiaohua, Zhang Li, Hong Weilong, Zeng Kang

机构信息

Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.

Department of Dermatology, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.

出版信息

Exp Ther Med. 2018 Feb;15(2):1803-1808. doi: 10.3892/etm.2017.5634. Epub 2017 Dec 14.

Abstract

The present study aimed to determine the expression of microRNA (miR)-222 in hypertrophic scar (HS) tissues, and investigate the regulatory mechanism of miR-222 in HS. A total of 36 patients diagnosed with HS between August 2013 and May 2016 were included in the present study. HS tissues and HS-adjacent tissues were collected from patients. Primary fibroblasts were obtained from HS tissue. Reverse transcription-quantitative polymerase chain reaction was used to measure mRNA levels of matrix metalloproteinase 1 (MMP1) and miR-222. Western blotting was conducted to determine MMP1 expression and an MTT assay was performed to measure the viability of fibroblasts. A dual luciferase reporter assay was used to identify the binding of miR-222 to MMP1 mRNA. It was demonstrated that MMP1 serves a role in HS at the transcription level and that increased MMP1 expression inhibited the viability of fibroblasts. miR-222 serves a regulatory role in HS by targeting its target gene MMP1 and regulates the expression of MMP1 by binding to its 3'-untranslated region. The decreased expression of miR-222 suppresses the viability of fibroblasts by regulating MMP1 expression. The present study demonstrated that the downregulation of MMP1 in HS tissues is associated with the upregulation of miR-222 expression. miR-222 may therefore regulate the viability of fibroblasts in HS and the expression of related proteins via MMP1.

摘要

本研究旨在确定微小RNA(miR)-222在增生性瘢痕(HS)组织中的表达,并探讨miR-222在HS中的调控机制。本研究纳入了2013年8月至2016年5月期间共36例诊断为HS的患者。从患者身上采集HS组织和HS旁组织。从HS组织中获取原代成纤维细胞。采用逆转录-定量聚合酶链反应检测基质金属蛋白酶1(MMP1)和miR-222的mRNA水平。进行蛋白质印迹法以确定MMP1的表达,并进行MTT试验以检测成纤维细胞的活力。采用双荧光素酶报告基因测定法鉴定miR-222与MMP1 mRNA的结合。结果表明,MMP1在转录水平上参与HS的发生发展,MMP1表达增加抑制成纤维细胞的活力。miR-222通过靶向其靶基因MMP1在HS中发挥调控作用,并通过与其3'-非翻译区结合来调节MMP1的表达。miR-222表达降低通过调节MMP1的表达抑制成纤维细胞的活力。本研究表明,HS组织中MMP1的下调与miR-222表达上调有关。因此,miR-222可能通过MMP1调节HS中成纤维细胞的活力和相关蛋白的表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1736/5776557/d58b5830324e/etm-15-02-1803-g00.jpg

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