Sporadic inclusion body myositis-derived myotube culture revealed muscle cell-autonomous expression profiles.

Autor: Suzuki N; Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan.; Department of Rehabilitation Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan., Kanzaki M; Graduate School of Biomedical Engineering, Tohoku University, Sendai, Japan., Koide M; Department of Orthopedic Surgery, Graduate School of Medicine, Tohoku University, Sendai, Japan., Izumi R; Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan., Fujita R; Department of Orthopedic Surgery, Graduate School of Medicine, Tohoku University, Sendai, Japan., Takahashi T; Department of Orthopedic Surgery, Graduate School of Medicine, Tohoku University, Sendai, Japan., Ogawa K; Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan.; Department of Orthopedic Surgery, Graduate School of Medicine, Tohoku University, Sendai, Japan., Yabe Y; Department of Orthopedic Surgery, Graduate School of Medicine, Tohoku University, Sendai, Japan., Tsuchiya M; Department of Nursing, Tohoku Fukushi University, Sendai, Japan., Suzuki M; Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan., Harada R; Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan., Ohno A; Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan., Ono H; Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan.; Department of Neurology, National Hospital Organization Iwate Hospital, Ichinoseki, Iwate, Japan., Nakamura N; Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan., Ikeda K; Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan., Warita H; Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan., Osana S; Division of Biomedical Engineering for Health and Welfare, Graduate School of Biomedical Engineering, Tohoku University, Sendai, Japan., Oikawa Y; Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Japan.; Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan., Toyohara T; Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.; Department of Medical Science, Tohoku University Graduate School of Biomedical Engineering, Sendai, Japan., Abe T; Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.; Department of Medical Science, Tohoku University Graduate School of Biomedical Engineering, Sendai, Japan.; Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine, Sendai, Japan., Rui M; Department of Rehabilitation Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan., Ebihara S; Department of Rehabilitation Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan., Nagatomi R; Division of Biomedical Engineering for Health and Welfare, Graduate School of Biomedical Engineering, Tohoku University, Sendai, Japan., Hagiwara Y; Department of Orthopedic Surgery, Graduate School of Medicine, Tohoku University, Sendai, Japan., Aoki M; Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 Aug 01; Vol. 19 (8), pp. e0306021. Date of Electronic Publication: 2024 Aug 01 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0306021
Abstrakt: Sporadic inclusion body myositis (sIBM) is a muscle disease in older people and is characterized by inflammatory cell invasion into intact muscle fibers and rimmed vacuoles. The pathomechanism of sIBM is not fully elucidated yet, and controversy exists as to whether sIBM is a primary autoimmune disease or a degenerative muscle disease with secondary inflammation. Previously, we established a method of collecting CD56-positive myoblasts from human skeletal muscle biopsy samples. We hypothesized that the myoblasts derived from these patients are useful to see the cell-autonomous pathomechanism of sIBM. With these resources, myoblasts were differentiated into myotubes, and the expression profiles of cell-autonomous pathology of sIBM were analyzed. Myoblasts from three sIBM cases and six controls were differentiated into myotubes. In the RNA-sequencing analysis of these "myotube" samples, 104 differentially expressed genes (DEGs) were found to be significantly upregulated by more than twofold in sIBM, and 13 DEGs were downregulated by less than twofold. For muscle biopsy samples, a comparative analysis was conducted to determine the extent to which "biopsy" and "myotube" samples differed. Fifty-three DEGs were extracted of which 32 (60%) had opposite directions of expression change (e.g., increased in biopsy vs decreased in myotube). Apolipoprotein E (apoE) and transmembrane protein 8C (TMEM8C or MYMK) were commonly upregulated in muscle biopsies and myotubes from sIBM. ApoE and myogenin protein levels were upregulated in sIBM. Given that enrichment analysis also captured changes in muscle contraction and development, the triggering of muscle atrophy signaling and abnormal muscle differentiation via MYMK or myogenin may be involved in the pathogenesis of sIBM. The presence of DEGs in sIBM suggests that the myotubes formed from sIBM-derived myoblasts revealed the existence of muscle cell-autonomous degeneration in sIBM. The catalog of DEGs will be an important resource for future studies on the pathogenesis of sIBM focusing on primary muscle degeneration.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Suzuki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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