Role of microRNAs derived from dermal microvascular endothelial cells in the pathogenesis of systemic scleroderma.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17776
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Kumamoto University
• Principal Investigator: Makino Katsunari 熊本大学, 大学院生命科学研究部(医), 特任准教授 (00433037)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 全身性強皮症 / 皮膚血管内皮細胞 / microRNA

Outline of Final Research Achievements

Systemic sclerosis (SSc) is an acquired disorder characterized by the fibrosis of the skin and internal organs. Although the pathogenesis of this disease is still unclear, it includes vascular damage, fibrosis, and auto-immune disorder. In this study, we compared the microRNA expression profile in cultured dermal microvascular endothelial cells (ECs) of SSc with that of healthy control. Upon comparison of the expression of microRNA between SSc and healthy control EC, miR-155, miR-221 and miR-222 were found to be significantly upregulated in SSc EC. The overexpression of miR-155, miR-221 or miR-222 in human dermal EC led to the induction of mesenchymal cell markers FSP1 and ACTA2, whereas led to the reduction of endothelial cell markers vWF. Also, we found the overexpression of miR-221 blocked the endothelial cell tube formation. Our data indicate that understanding miRNA signaling of endothelial cells may lead to a therapeutic approach for SSc.

Free Research Field

皮膚科学、リウマチ病学

Academic Significance and Societal Importance of the Research Achievements

全身性強皮症は皮膚をはじめ他臓器に線維化を生じる疾患であり、線維化、自己免疫異常、血管障害などの病態が複雑に関与するとされる。血管障害としては、レイノー症状や指潰瘍などの症状が知られているが、血管障害の機序は明らかになっていない。本研究では、血管障害にマイクロRNAの異常が関与しているか検討を行った。全身性強皮症の皮膚から血管内皮細胞を培養し、マイクロRNAの発現を健常人と比較した結果、miR-155、miR-221、miR-222が全身性強皮症で上昇していることを見出した。本研究により、全身性強皮症の血管障害へマイクロRNAの異常が関与する可能性が示唆された。