Metabolome and transcriptome analysis on muscle of sporadic inclusion body myositis
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...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-10-01
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| Series: | Annals of Clinical and Translational Neurology |
| Online Access: | https://doi.org/10.1002/acn3.51657 |
| _version_ | 1811345045152858112 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Ayuka Murakami |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T19:57:11Z |
| format | Article |
| id | doaj.art-3b07e9ffabbe43e98c89603134aaff9c |
| institution | Directory Open Access Journal |
| issn | 2328-9503 |
| language | English |
| last_indexed | 2024-04-13T19:57:11Z |
| publishDate | 2022-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Annals of Clinical and Translational Neurology |
| spelling | doaj.art-3b07e9ffabbe43e98c89603134aaff9c2022-12-22T02:32:18ZengWileyAnnals of Clinical and Translational Neurology2328-95032022-10-019101602161510.1002/acn3.51657Metabolome and transcriptome analysis on muscle of sporadic inclusion body myositisAyuka Murakami0Seiya Noda1Tomoyuki Kazuta2Satoko Hirano3Seigo Kimura4Hirotaka Nakanishi5Koji Matsuo6Koyo Tsujikawa7Madoka Iida8Haruki Koike9Kazuma Sakamoto10Yuichiro Hara11Satoshi Kuru12Kenji Kadomatsu13Teppei Shimamura14Tomoo Ogi15Masahisa Katsuno16Department of Neurology Nagoya University Graduate School of Medicine Nagoya JapanDepartment of Neurology Nagoya University Graduate School of Medicine Nagoya JapanDepartment of Neurology Nagoya University Graduate School of Medicine Nagoya JapanDepartment of Neurology Nagoya University Graduate School of Medicine Nagoya JapanDepartment of Neurology Nagoya University Graduate School of Medicine Nagoya JapanDepartment of Neurology Yokkaichi Municipal Hospital Yokkaichi JapanDepartment of Neurology Kariya Toyota General Hospital Kariya JapanDepartment of Neurology Nagoya University Graduate School of Medicine Nagoya JapanDepartment of Neurology Nagoya University Graduate School of Medicine Nagoya JapanDepartment of Neurology Nagoya University Graduate School of Medicine Nagoya JapanDepartment of Biochemistry Nagoya University Graduate School of Medicine Nagoya JapanDepartment of Genetics Research Institute of Environmental Medicine (RLeM), Nagoya University Nagoya JapanDepartment of Neurology National Hospital Organization Suzuka Hospital Suzuka JapanDepartment of Biochemistry Nagoya University Graduate School of Medicine Nagoya JapanDivision of Systems Biology Nagoya University Graduate School of Medicine Nagoya JapanDepartment of Genetics Research Institute of Environmental Medicine (RLeM), Nagoya University Nagoya JapanDepartment of Neurology Nagoya University Graduate School of Medicine Nagoya JapanAbstract 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.https://doi.org/10.1002/acn3.51657 |
| spellingShingle | 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 Metabolome and transcriptome analysis on muscle of sporadic inclusion body myositis Annals of Clinical and Translational Neurology |
| title | Metabolome and transcriptome analysis on muscle of sporadic inclusion body myositis |
| title_full | Metabolome and transcriptome analysis on muscle of sporadic inclusion body myositis |
| title_fullStr | Metabolome and transcriptome analysis on muscle of sporadic inclusion body myositis |
| title_full_unstemmed | Metabolome and transcriptome analysis on muscle of sporadic inclusion body myositis |
| title_short | Metabolome and transcriptome analysis on muscle of sporadic inclusion body myositis |
| title_sort | metabolome and transcriptome analysis on muscle of sporadic inclusion body myositis |
| url | https://doi.org/10.1002/acn3.51657 |
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