Overexpression of miR-101 suppresses collagen synthesis by targeting EZH2 in hypertrophic scar fibroblasts

Jie Li; Yan Li; Yunchuan Wang; Xiang He; Jing Wang; Weixia Cai; Yanhui Jia; Dan Xiao; Jian Zhang; Ming Zhao; Kuo Shen; Zichao Li; Wenbin Jia; Kejia Wang; Yue Zhang; Linlin Su; Huayu Zhu; Dahai Hu

doi:10.1093/burnst/tkab038

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Overexpression of miR-101 suppresses collagen synthesis by targeting EZH2 in hypertrophic scar fibroblasts

更新时间：2022-06-14

- Overexpression of miR-101 suppresses collagen synthesis by targeting EZH2 in hypertrophic scar fibroblasts
- Burns & Trauma Vol. 9, Issue 1, (2021)
- 作者机构：
  
  1. Department of Burns and Cutaneous Surgery
  2. Fourth Military Medical University
- 作者简介：
- 基金信息：
- DOI：10.1093/burnst/tkab038
  CLC：
- Published：2021，
  
  Published Online：26 November 2021，
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Jie Li, Yan Li, Yunchuan Wang, Xiang He, Jing Wang, Weixia Cai, Yanhui Jia, Dan Xiao, Jian Zhang, Ming Zhao, Kuo Shen, Zichao Li, Wenbin Jia, Kejia Wang, Yue Zhang, Linlin Su, Huayu Zhu, Dahai Hu, Overexpression of miR-101 suppresses collagen synthesis by targeting EZH2 in hypertrophic scar fibroblasts, Burns & Trauma, Volume 9, 2021, tkab038, https://doi.org/10.1093/burnst/tkab038
DOI：

Jie Li, Yan Li, Yunchuan Wang, Xiang He, Jing Wang, Weixia Cai, Yanhui Jia, Dan Xiao, Jian Zhang, Ming Zhao, Kuo Shen, Zichao Li, Wenbin Jia, Kejia Wang, Yue Zhang, Linlin Su, Huayu Zhu, Dahai Hu, Overexpression of miR-101 suppresses collagen synthesis by targeting EZH2 in hypertrophic scar fibroblasts, Burns & Trauma, Volume 9, 2021, tkab038, https://doi.org/10.1093/burnst/tkab038 DOI：

摘要

Abstract

BackgroundMicroRNA-101 (miR-101) is a tumor suppressor microRNA (miRNA) and its loss is associated with the occurrence and progression of various diseases. However

the biological function and target of miR-101 in the pathogenesis of hypertrophic scars (HS) remains unknown.MethodsWe harvested HS and paired normal skin (NS) tissue samples from patients and cultured their fibroblasts (HSF and NSF

respectively). We used quantitative reverse transcriptase polymerase chain reaction (qRT-PCR)

fluorescence in situ hybridization (FISH)

enzyme-linked immunosorbent assays (ELISA) and Western blot analyses to measure mRNA levels and protein expression of miR-101

enhancer of zeste homolog 2 (EZH2)

collagen 1 and 3 (Col1 and Col3) and α-smooth muscle actin (α-SMA) in different in vitro conditions. We also used RNA sequencing to evaluate the relevant signaling pathways and bioinformatics analysis and dual-luciferase reporter assays to predict miR-101 targets. We utilized a bleomycin-induced fibrosis mouse model in which we injected miR-101 mimics to evaluate collagen deposition in vivo.ResultsWe found low expression of miR-101 in HS and HSF compared to NS and NSF. Overexpressing miR-101 decreased Col1

Col3 and α-SMA expression in HSF. We detected high expression of EZH2 in HS and HSF. Knockdown of EZH2 decreased Col1

Col3 and α-SMA in HSF. Mechanistically

miR-101 targeted the 3′-untranslated region (3′UTR) of EZH2

as indicated by the decreased expression of EZH2. Overexpressing EZH2 rescued miR-101-induced collagen repression. MiR-101 mimics effectively suppressed collagen deposition in the bleomycin-induced fibrosis mouse model.ConclusionsOur data reveal that miR-101 targets EZH2 in HS collagen production

providing new insight into the pathological mechanisms underlying HS formation.

关键词

Keywords

Hypertrophic scarsmiR-101EZH2FibroblastsskinCollagen

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