TGF-β regulates TGFBIp expression in corneal fibroblasts via miR-21, miR-181a, and Smad signaling

• Published in: Biochemical and biophysical research communications 2016-03, Vol.472 (1), p.150-155
• Main Authors: Choi, Seung-il, Jin, Jun-Yup, Maeng, Yong-Sun, Kim, Tae-im, Kim, Eung Kweon
• Format: Article
• Language: English
• Subjects: Cells, Cultured; Cornea - cytology; Cornea - metabolism; Corneal Dystrophies, Hereditary - genetics; Corneal Dystrophies, Hereditary - metabolism; Corneal Dystrophies, Hereditary - pathology; Corneal fibroblasts; Extracellular Matrix Proteins - genetics; Extracellular Matrix Proteins - metabolism; Fibroblasts - cytology; Fibroblasts - metabolism; Gene Expression Regulation; Granular corneal dystrophy type 2; Homozygote; Humans; microRNA; MicroRNAs - genetics; MicroRNAs - metabolism; Models, Biological; Mutant Proteins - genetics; Mutant Proteins - metabolism; Point Mutation; RNA, Messenger - genetics; RNA, Messenger - metabolism; Signal Transduction; Smad Proteins - metabolism; TGF-β; TGFBI; TGFBIp; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - metabolism; Transforming Growth Factor beta1 - metabolism
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2016.02.086

Transforming growth factor-β (TGF-β)-induced gene (TGFBI) protein (TGFBIp) is associated with granular corneal dystrophy type 2 (GCD2). TGFBIp levels can affect GCD2 phenotypes, but the underlying molecular mechanisms have not been fully elucidated. We investigated the involvement of microRNA (miRNA) and TGF-β in the regulation of TGFBIp expression in corneal fibroblasts. Ectopic expression of miR-9, miR-21, and miR-181a significantly decreased TGFBIp levels. Conversely, expression of miR-21 and miR-181a was induced by TGF-β1. Expression of miR-21 was 10-fold higher than that of miR-9 and miR-181a in corneal fibroblasts. Additionally, TGF-β1 expression was significantly higher than that of TGF-β2 and TGF-β3 in corneal fibroblasts, whereas expression of all three TGF-β forms was not significantly different between wild-type (WT) and GCD2 homozygotes (HO) corneal fibroblasts. Taken together, these data indicate that TGFBIp expression is positively regulated by TGF-β, whereas TGF-β-induced miR-21 and miR-181a negatively regulate TGFBIp expression. In conclusion, TGFBIp levels in corneal fibroblasts are controlled via the coordinated activity of miR-21 and miR-181a and by Smad signaling. Pharmacologic modulation of these miRNAs and TGF-β signaling could have therapeutic potential for TGFBI-associated corneal dystrophy, including GCD2. •TGFBIp is regulated by miR-9, miRNA-21, and miR-181a in corneal fibroblasts.•TGF-β1 induces miRNA-21, miR-181a, and TGFBIp in corneal fibroblasts.•TGFBIp is positively regulated by TGF-β1 and negatively by miRNA-21 and miR-181a.•These miRNAs represent potential therapeutic targets for corneal dystrophy.