MicroRNA expression abnormalities in limited cutaneous scleroderma and diffuse cutaneous scleroderma.
Scleroderma (systemic sclerosis, SSc) is a complex autoimmune disease caused by progressive fibrotic replacement of normal tissue architecture, a progressive and ultimately fatal process that currently has no cure. Although dysregulation of microRNAs (miRNAs) is known to be involved in a variety of pathophysiologic processes, the role of miRNAs in SSc is unclear. In comparison with the normal skin tissues, miRNAs were aberrantly expressed in limited cutaneous scleroderma and diffuse cutaneous scleroderma skin tissues. We also identified miRNAs whose expressions were correlated with SSc fibrosis: miR-21, miR-31, miR-146, miR-503, miR-145, and miR-29b were predicted to be involved. This study further confirmed that miR-21 was increased whereas miR-145 and miR-29b were decreased both in the skin tissues and fibroblasts. As predicted target genes, SMAD7, SAMD3, and COL1A1 were regulated by these miRNAs. After stimulation with transforming growth factor β, the expression of miR-21 was increased and that of SMAD7 mRNA was decreased. MiR-145 was upregulated whereas the mRNA level of SMAD3 was downregulated. The downregulation of miR-29b was correlated with the upregulation of COL1A1 mRNA. MiRNAs might play an important role in the pathogenesis of SSc and suggest a potential therapy.
Department of Rheumatology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China.
Honglin
H
Zhu
Yisha
Y
Li
Shunlin
S
Qu
Hui
H
Luo
Yaou
Y
Zhou
Yanping
Y
Wang
Hongjun
H
Zhao
Yunhui
Y
You
Xianzhong
X
Xiao
Xiaoxia
X
Zuo
D000328:Adult; D024042:Collagen Type I / Q000235:genetics; D000090602:Collagen Type I, alpha 1 Chain; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D045743:Scleroderma, Diffuse / Q000235:genetics*; D045745:Scleroderma, Limited / Q000235:genetics*; D051900:Smad3 Protein / Q000235:genetics; D051906:Smad7 Protein / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D055815:Young Adult
D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D035683:MicroRNAs; D012333:RNA, Messenger; C497790:SMAD3 protein, human; C497806:SMAD7 protein, human; D051900:Smad3 Protein; D051906:Smad7 Protein; D016212:Transforming Growth Factor beta