Transcriptome analysis for the fascia as a target organ in dermatomyositis

• Project/Area Number: 17K09985
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Yoshida Ken 東京慈恵会医科大学, 医学部, 講師 (20398796)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 皮膚筋炎 / 多発性筋炎 / 筋膜 / 筋膜炎 / 網羅的遺伝子解析

Outline of Final Research Achievements

Our previous studies showed by en bloc biopsy combined with MRI that inflammatory cell infiltration progressed from the fascia into the muscle in patients with dermatomyositis (DM). We aimed to investigate more highly expressed genes in the fascia of patients with DM compared with polymyositis (PM). Frozen sections from biopsied tissues were divided into the fascia and muscle, and total RNA was extracted from each tissue. The total RNA obtained from each tissue was analyzed by RNA sequencing. No significant difference found in expressed genes in the muscle between patients with DM and PM. We found that the levels of expressed genes including chemokines and transcription factors were significantly higher in the fascia of patients with DM compared with PM.

Academic Significance and Societal Importance of the Research Achievements

皮膚筋炎の治療は、現在においてもステロイド薬と免疫抑制薬が中心であり、これらの薬剤を投与しても再発例や難治例が多く、病態解明が急務である。また、長期薬剤投与による副作用も問題となる。本研究結果から通常筋膜炎を伴わない多発性筋炎由来筋膜組織と比較して皮膚筋炎由来筋膜組織において、有意に高発現している多くの遺伝子が検出された。今後、これら病態候補遺伝子の発現部位や発現細胞種など更なる研究により皮膚筋炎の病態解明が進めば、それらの病態関連因子を標的とした新たな治療開発につながる可能性があり、意義深いと考えられる。