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


CONCLUSIONS
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.
Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, Japan. mjin@kumamoto-u.ac.jp
Takaomi
T
Sing
Masatoshi
M
Jinnin
Keitaro
K
Yamane
Norihito
N
Honda
Kastunari
K
Makino
Ikko
I
Kajihara
Takamitsu
T
Makino
Keisuke
K
Sakai
Shinichi
S
Masuguchi
Satoshi
S
Fukushima
Hironobu
H
Ihn
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D003882:Dermatomyositis / Q000097:blood; D020405:Dermis / Q000378:metabolism / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000235:genetics / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000097:blood; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D034741:RNA, Small Interfering / Q000235:genetics; D045743:Scleroderma, Diffuse / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D012594:Scleroderma, Localized / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics
D015415:Biomarkers; D039302:Integrin alphaVbeta3; C541874:MIRN92 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D016212:Transforming Growth Factor beta; D020781:Matrix Metalloproteinase 1