Department of Rheumatology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China.
J Clin Immunol. 2012 Jun;32(3):514-22. doi: 10.1007/s10875-011-9647-y. Epub 2012 Feb 4.
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.
硬皮病（系统性硬皮病，SSc）是一种复杂的自身免疫性疾病，由正常组织结构的进行性纤维化替代引起，是一个进行性的、最终致命的过程，目前尚无治愈方法。尽管已知 microRNAs（miRNAs）的失调参与了多种病理生理过程，但 miRNAs 在 SSc 中的作用尚不清楚。与正常皮肤组织相比，局限性硬皮病和弥漫性硬皮病皮肤组织中 miRNAs 的表达出现异常。我们还鉴定了与 SSc 纤维化相关的表达受调控的 miRNAs：miR-21、miR-31、miR-146、miR-503、miR-145 和 miR-29b 被预测为参与其中。本研究进一步证实，miR-21 在皮肤组织和成纤维细胞中均增加，而 miR-145 和 miR-29b 均减少。作为预测的靶基因，SMAD7、SAMD3 和 COL1A1 受这些 miRNAs 调节。转化生长因子 β 刺激后，miR-21 的表达增加，SMAD7 mRNA 的表达减少。miR-145 上调，而 SMAD3 mRNA 的表达下调。miR-29b 的下调与 COL1A1 mRNA 的上调相关。miRNAs 可能在 SSc 的发病机制中发挥重要作用，并提示一种潜在的治疗方法。
