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The mechanisms of transcriptional regulation by microRMAs in relation to COLIA2 promotor region in keloid

瘢痕疙瘩中 microRMAs 与 COLIA2 启动子区相关的转录调控机制

基本信息

批准号：
22592003
负责人：
SHIMIZU Hajime
金额：
$ 2.16万
依托单位：
Nippon Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2010
资助国家：
日本
起止时间：
2010 至 2012
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22592003/
关键词：
ケロイド microRNA 線維化 IL-6 コラーゲン micrpRNA

项目摘要

We aimed to investigate expression profiles of microRNAs (miRNAs) in order to understanding the molecular mechanism(s) involved in the pathogenesis of keloid. We confirmed that miR-10a was significantly under-expressed in keloid fibroblasts (KFs) compared with normal dermal fibroblasts (NFs).Inhibition and induction of miR-10a respectively by miRNA inhibitor and retinoic acid (RA) in KFs and NFs revealed that IL-6 and pro-collagen type I (PICP) secretions in the culture supernatants were decreased by miR-10a inhibitor and increased by RA treatment. These results suggest that miR-10a regulates the synthesis and secretion of collagen in KFs and NFs. KF and NF cells were transfected with miR-10a oligonucleotide. The secretion of PICP was reduced in miR-10a transfected KFs and NFs. The miR-10a was significantly over-expressed in KFs and NFs after treatment with RA. The treated cells were harvested for miR-10a qPCR assay and the culture supernatant was analyzed for IL-6 and PICP secretion by ELISA method. The assays indicated that IL-6 concentrations were markedly increased in KFs compared with NFs after RA treatment.Our data confirmed the differential expression of miR-10a in KFs compared with NFs. The miR-10a regulates the synthesis and secretion of collagen in KFs and NFs. Down-regulation of miR-10a may be one of the mechanisms by which collagen is highly deposited in KFs. Our results showed that miR-10a is a promising new effective strategy for targeting keloid lesions.

本研究旨在探讨瘢痕疙瘩中microRNAs（miRNAs）的表达谱，以了解瘢痕疙瘩发病的分子机制。与正常皮肤成纤维细胞（NF）相比，瘢痕疙瘩成纤维细胞（KFs）中miR-10a的表达显著降低; miR-10a抑制剂和维甲酸（RA）分别抑制和诱导KFs和NF中miR-10a的表达，结果显示miR-10a抑制剂可降低KFs和NF培养上清中IL-6和I型前胶原（PICP）的分泌，而RA处理可增加KFs和NF培养上清中PICP的分泌。这些结果表明，miR-10a调节KFs和NF中胶原的合成和分泌。用miR-10a寡核苷酸转染KF和NF细胞。miR-10a转染的KFs和NF中PICP的分泌减少。RA治疗后，KFs和NF中miR-10a显著过表达。收获经处理的细胞用于miR-10a qPCR测定，并通过ELISA方法分析培养物上清液的IL-6和PICP分泌。结果表明，RA治疗后，KFs中IL-6的浓度明显高于NF，证实了miR-10a在KFs和NF中的差异表达。miR-10a调节KFs和NF中胶原的合成和分泌。miR-10a的下调可能是胶原蛋白在KFs中高度沉积的机制之一。我们的研究结果表明，miR-10a是一个有前途的新的有效的战略，针对瘢痕疙瘩病变。