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miR-196a Downregulation Increases the Expression of Type I and III Collagens in Keloid Fibroblasts

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Title: miR-196a Downregulation Increases the Expression of Type I and III Collagens in Keloid Fibroblasts
Authors: Kashiyama, Kazuya / Mitsutake, Norisato / Matsuse, Michiko / Ogi, Tomoo / Saenko, Vladimir A / Ujifuku, Kenta / Utani, Atsushi / Hirano, Akiyoshi / Yamashita, Shunichi
Issue Date: Jun-2012
Publisher: Nature Publishing Group
Citation: Journal of Investigative Dermatology, 132(6), pp.1597-1604; 2012
Abstract: Keloids are a fibroproliferative disease due to abnormal wound healing process after skin injury. They are characterized by overproduction of extracellular matrix (ECM) such as collagens. MicroRNAs (miRNAs) are noncoding small RNAs and negatively regulate protein expression. Several miRNAs that have critical roles in tissue fibrosis and ECM metabolism have been reported. However, regulation and function of miRNAs in keloid remain to be explored. The purpose of this study was to identify miRNAs involved in keloid pathogenesis. We performed miRNA microarray analysis to compare miRNA expression profiles between keloid-derived fibroblasts (KFs) and normal fibroblasts (NFs). In all, 7 upregulated and 20 downregulated miRNAs were identified. Among these, we focused on miR-196a, which showed the highest fold change. Overexpression or knockdown of miR-196a led to a decreased or increased level of secreted type I/III collagens, respectively. Reporter analysis showed direct binding of miR-196a to the 3′ untranslated region (UTR) of COL1A1 and COL3A1. In conclusion, we demonstrate for the first time that miRNA expression profile is altered in KFs compared with NFs. Downregulation of miR-196a may be one of the mechanisms by which collagens are highly deposited in keloid tissues. Our findings suggest that miR-196a could be a new therapeutic target for keloid lesions.
Keywords: collagen type 1 / collagen type 3 / corticosteroid / microRNA / microRNA 196a / tranilast / unclassified drug / 3' untranslated region / acne / adolescent / adult / aged / article / blister / clinical article / controlled study / down regulation / electron therapy / female / fibroblast / human / human cell / human tissue / keloid / male / microarray analysis / pathogenesis / priority journal / protein expression / RNA binding / skin surgery / upregulation / Adolescent / Aged, 80 and over / Collagen Type I / Collagen Type III / CpG Islands / Dermis / DNA Methylation / Down-Regulation / Female / Fibroblasts / Luciferases / Middle Aged / Primary Cell Culture / Promoter Regions / Genetic / Real-Time Polymerase Chain Reaction / Young Adult
URI: http://hdl.handle.net/10069/29204
ISSN: 0022202X
DOI: 10.1038/jid.2012.22
Rights: © 2012 The Society for Investigative Dermatology.
Type: Journal Article
Text Version: author
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/29204

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