title: miR-196a downregulation increases the expression of type I and III collagens in keloid fibroblasts.
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.
authors.affiliation: Department of Radiation Medical Sciences, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kashiyama
authors.forename: Norisato
authors.initials: N
authors.lastname: Mitsutake
authors.forename: Michiko
authors.initials: M
authors.lastname: Matsuse
authors.forename: Tomoo
authors.initials: T
authors.lastname: Ogi
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Saenko
authors.forename: Kenta
authors.initials: K
authors.lastname: Ujifuku
authors.forename: Atsushi
authors.initials: A
authors.lastname: Utani
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Hirano
authors.forename: Shunichi
authors.initials: S
authors.lastname: Yamashita
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D024042:Collagen Type I / Q000235:genetics*; D024061:Collagen Type III / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000502:physiology; D020405:Dermis / Q000166:cytology; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D006801:Humans; D007627:Keloid / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D008156:Luciferases / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D061251:Primary Cell Culture; D011401:Promoter Regions, Genetic / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; C542543:MIRN196 microRNA, human; D035683:MicroRNAs; D008156:Luciferases