Metabolome and transcriptome analysis on muscle of sporadic inclusion body myositis.
Metabolome and transcriptome analysis on muscle of sporadic inclusion body myositis.
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DOI：
10.1002/acn3.51657
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发表时间：
2022-10
影响因子：
5.3
通讯作者：
Katsuno, Masahisa
中科院分区：
文献类型：
--
作者：
Murakami, Ayuka;Noda, Seiya;Kazuta, Tomoyuki;Hirano, Satoko;Kimura, Seigo;Nakanishi, Hirotaka;Matsuo, Koji;Tsujikawa, Koyo;Iida, Madoka;Koike, Haruki;Sakamoto, Kazuma;Hara, Yuichiro;Kuru, Satoshi;Kadomatsu, Kenji;Shimamura, Teppei;Ogi, Tomoo;Katsuno, Masahisa
散发性包涵体肌炎（sIBM）是50岁以上患者中最常见的获得性肌病。sIBM对任何免疫抑制疗法几乎没有反应，并且其病理生理学仍然不清楚。本研究旨在探索sIBM的致病途径，并确定新的治疗靶点，使用代谢组学和转录组学分析。在这项回顾性观察性研究中，我们分析了14名sIBM患者和6名非疾病受试者的活检肌肉样本，以确定代谢特征。采用毛细管电泳飞行时间质谱的阳离子和阴离子模式对冷冻肌肉样品进行代谢物测定。我们通过RNA测序和组织病理学研究验证了sIBM患者肌肉中代谢途径的改变。共鉴定出198种代谢产物。代谢组学和转录组学分析确定了sIBM肌肉样品中的特定代谢物变化。组胺生物合成和某些糖胺聚糖生物合成的途径上调sIBM患者，而肉毒碱代谢和肌酸代谢下调。组织学检查显示骨骼肌样本中肥大细胞浸润和硫酸软骨素沉积，支持代谢组学和转录组学分析的结果。我们确定了sIBM患者肌肉样本中几种代谢途径的改变。这些结果表明，肥大细胞，硫酸软骨素的生物合成，肉毒碱，肌酸发挥作用sIBM的病理生理。
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. 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. 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. 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.
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DOI：
10.1093/bioinformatics/btq033
发表时间：
2010-03-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Quinlan AR;Hall IM
通讯作者：
Hall IM
影响因子：
7.4
作者：
Soga, T;Heiger, DN
通讯作者：
Heiger, DN
影响因子：
9.8
作者：
Choi, Jin Woo;Ohn, Jung Hun;Park, Kyong Soo
通讯作者：
Park, Kyong Soo
影响因子：
11.2
作者：
Larman, H. Benjamin;Salajegheh, Mohammad;Greenberg, Steven A.
通讯作者：
Greenberg, Steven A.
影响因子：
14.5
作者：
Benveniste, Olivier;Guiguet, Marguerite;Hilton-Jones, David
通讯作者：
Hilton-Jones, David