TY - JOUR
T1 - Sporadic inclusion body myositis-derived myotube culture revealed muscle cell-autonomous expression profiles
AU - Suzuki, Naoki
AU - Kanzaki, Makoto
AU - Koide, Masashi
AU - Izumi, Rumiko
AU - Fujita, Ryo
AU - Takahashi, Tadahisa
AU - Ogawa, Kazumi
AU - Yabe, Yutaka
AU - Tsuchiya, Masahiro
AU - Suzuki, Masako
AU - Harada, Ryuhei
AU - Ohno, Akiyuki
AU - Ono, Hiroya
AU - Nakamura, Naoko
AU - Ikeda, Kensuke
AU - Warita, Hitoshi
AU - Osana, Shion
AU - Oikawa, Yoshitsugu
AU - Toyohara, Takafumi
AU - Abe, Takaaki
AU - Rui, Muliang
AU - Ebihara, Satoru
AU - Nagatomi, Ryoichi
AU - Hagiwara, Yoshihiro
AU - Aoki, Masashi
N1 - Publisher Copyright:
Copyright: © 2024 Suzuki et al.
PY - 2024/8
Y1 - 2024/8
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0306021
DO - 10.1371/journal.pone.0306021
M3 - Article
C2 - 39088432
AN - SCOPUS:85200148108
SN - 1932-6203
VL - 19
JO - PLoS ONE
JF - PLoS ONE
IS - 8 August
M1 - e0306021
ER -