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論文
- タイトル
- タイトル（英）
- Metabolome and transcriptome analysis on muscle of sporadic inclusion body myositis
- 参照URL
- https://researchmap.jp/yuichirohara/published_papers/43817071
- 著者
- 著者（英）
- Ayuka Murakami,Seiya Noda,Tomoyuki Kazuta,Satoko Hirano,Seigo Kimura,Hirotaka Nakanishi,Koji Matsuo,Koyo Tsujikawa,Madoka Iida,Haruki Koike,Kazuma Sakamoto,Yuichiro Hara,Satoshi Kuru,Kenji Kadomatsu,Teppei Shimamura,Tomoo Ogi,Masahisa Katsuno
- 担当区分
- 概要
- 概要（英）
- Abstract Objective Sporadic inclusion body myositis (sIBM) is the most common acquired myopathy in patients older than 50 years of age. sIBM is hardly responds to any immunosuppressing theraphies, and its pathophysiology remains elusive. This study aims to explore pathogenic pathways underlying sIBM and identify novel therapeutic targets using metabolomic and transcriptomic analyses. Methods In this retrospective observational study, we analyzed biopsied muscle samples from 14 sIBM patients and six non‐diseased subjects to identify metabolic profiles. Frozen muscle samples were used to measure metabolites with cation and anion modes of capillary electrophoresis time of flight mass spectrometry. We validated the metabolic pathway altered in muscles of sIBM patients through RNA sequencing and histopathological studies. Results A total of 198 metabolites were identified. Metabolomic and transcriptomic analyses identified specific metabolite changes in sIBM muscle samples. The pathways of histamine biosynthesis and certain glycosaminoglycan biosynthesis were upregulated in sIBM patients, whereas those of carnitine metabolism and creatine metabolism were downregulated. Histopathological examination showed infiltration of mast cells and deposition of chondroitin sulfate in skeletal muscle samples, supporting the results of metabolomic and transcriptomic analyses. Interpretation We identified alterations of several metabolic pathways in muscle samples of sIBM patients. These results suggest that mast cells, chondroitin sulfate biosynthesis, carnitine, and creatine play roles in sIBM pathophysiology.
- 出版者・発行元
- 出版者・発行元（英）
- Wiley
- 誌名
- 誌名（英）
- Annals of Clinical and Translational Neurology
- 巻
- 9
- 号
- 10
- 開始ページ
- 1602
- 終了ページ
- 1615
- 出版年月
- 2022年9月15日
- 査読の有無
- 招待の有無
- 掲載種別
- 研究論文（学術雑誌）
- ISSN
- 2328-9503
- DOI URL
- https://doi.org/10.1002/acn3.51657
- 共同研究・競争的資金等の研究課題
研究者
原 雄一郎
( )