microRNA-92a expression in the sera and dermal fibroblasts increases in patients with scleroderma

• Published in: Rheumatology (Oxford, England) Vol. 51; no. 9; pp. 1550 - 1556
• Main Authors: Sing, T., Jinnin, M., Yamane, K., Honda, N., Makino, K., Kajihara, I., Makino, T., Sakai, K., Masuguchi, S., Fukushima, S., Ihn, H.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.09.2012
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Biomarkers - blood; Cells, Cultured; Dermatomyositis - blood; Dermis - metabolism; Dermis - pathology; Diseases of the osteoarticular system; Female; Fibroblasts - metabolism; Fibroblasts - pathology; Gene Expression Regulation; Gene Silencing; Humans; Integrin alphaVbeta3 - genetics; Integrin alphaVbeta3 - metabolism; Lupus Erythematosus, Systemic - blood; Male; Matrix Metalloproteinase 1 - genetics; Matrix Metalloproteinase 1 - metabolism; Medical sciences; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; RNA, Small Interfering - genetics; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Scleroderma, Diffuse - blood; Scleroderma, Diffuse - diagnosis; Scleroderma, Diffuse - genetics; Scleroderma, Localized - blood; Scleroderma, Localized - diagnosis; Scleroderma, Localized - genetics; Transforming Growth Factor beta - genetics; Human; Immunopathology; Connective tissue disease; Skin disease; Rheumatology; Autoimmune disease; collagen disease; Polymerase chain reaction; Integrin; Collagen; Systemic disease; Serum; Molecular biology; Derm; Scleroderma; Fibroblast; PCR
• ISSN: 1462-0324; 1462-0332; 1462-0332
• DOI: 10.1093/rheumatology/kes120

microRNAs (miRNAs) play a part in various cellular activities. However, the role of miRNA in SSc is not fully understood. This study investigated the expression and role of miR-92a in SSc patients and evaluated the possibility that miR-92a is involved in the pathogenesis of this disease. Serum samples were obtained from 61 SSc patients. mRNAs were purified from serum and levels of miR-92a and miR-135 were measured with quantitative real-time PCR. miR-92a expression in dermal fibroblasts was also determined by quantitative real-time PCR. Immunoblotting was performed to detect MMP-1 protein. The median serum levels of miR-92a, not miR-135, were significantly higher in SSc patients than normal subjects. The constitutive up-regulated miR-92a expression was also found in cultured dermal fibroblasts from SSc skin, which was decreased by the transfection with siRNA of TGF-β. Furthermore, the forced overexpression of miR-92a in normal dermal fibroblasts using miR-92a mimic resulted in the down-regulation of MMP-1 expression. The increase of miR-92a in SSc may be due to the stimulation of intrinsic TGF-β activation seen in this disease. There is also a possibility that MMP-1 is the target of miR-92a and that increased miR-92a expression therefore plays a role in excessive collagen accumulation in SSc via the down-regulation of MMP-1. Clarifying the role of miRNAs in SSc may result in a better understanding of this disease and the development of new therapeutic approaches.