microRNA-92a expression in the sera and dermal fibroblasts increases in patients with scleroderma
T Sing, M Jinnin, K Yamane, N Honda, K Makino… - …, 2012 - academic.oup.com
T Sing, M Jinnin, K Yamane, N Honda, K Makino, I Kajihara, T Makino, K Sakai…
Rheumatology, 2012•academic.oup.comObjectives. 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. Methods. 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 …
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. Methods. 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 …
Abstract
Objectives. 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.
Methods. 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.
Results. 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.
Conclusion. 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.
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