RRC ID 52397
著者 Hosoyama T, Ichida S, Kanno M, Ishihara R, Hatashima T, Ueno K, Hamano K.
タイトル Microgravity influences maintenance of the human muscle stem/progenitor cell pool.
ジャーナル Biochem Biophys Res Commun
Abstract Microgravity induces skeletal muscle atrophy; however, the underlying mechanism is not clarified. In particular, the influence of microgravity on human skeletal muscle stem/progenitor cells (SMPCs) is not well understood. In this study, we used induced pluripotent stem cell-derived human SMPCs to investigate the effect of microgravity on maintenance of the stem/progenitor cell pool. Human SMPCs were induced by free-floating spherical aggregation culture, and derivatized-SMPC spheres were maintained in a microgravity condition (10-3 G) for 2 weeks using a clinostat rotation system. Microgravity culture deformed the SMPC spheres, with no signs of apoptosis. The most obvious change from microgravity culture was a significant decrease in the expression level of Pax7 in the SMPC spheres, with reduced numbers of myotubes in adhesion culture. Pax7 expression also decreased in the presence of the proteasome inhibitor MG132, indicating that the proteasomal degradation of Pax7 protein is not critical for its reduced expression in microgravity culture. Moreover, microgravity culture decreased the expression level of tumor necrosis factor receptor-associated factor 6 (TRAF6) and phosphorylation of its downstream molecule extracellular-related kinase (ERK) in SMPC spheres. Therefore, microgravity negatively regulates Pax7 expression in human SMPCs possibly through inhibition of the TRAF6/ERK pathway to consequently dysregulate SMPC pool maintenance. Overall, these results suggest that skeletal muscle atrophy is caused by microgravity-induced exhaustion of the stem cell pool.
巻・号 493(2)
ページ 998-1003
公開日 2017-11-18
DOI 10.1016/j.bbrc.2017.09.103
PII S0006-291X(17)31874-0
PMID 28942144
MeSH Cell Culture Techniques / instrumentation Cell Culture Techniques / methods* Cell Line Equipment Design Humans Induced Pluripotent Stem Cells / cytology Induced Pluripotent Stem Cells / metabolism MAP Kinase Signaling System Muscle, Skeletal / cytology* Muscle, Skeletal / metabolism PAX7 Transcription Factor / analysis PAX7 Transcription Factor / metabolism Stem Cells / cytology* Stem Cells / metabolism Weightlessness*
IF 2.985
引用数 7
リソース情報
ヒト・動物細胞 201B7(HPS0063)