論文 - 詳細
| RRC ID | 64995 |
|---|---|
| 著者 | Yasutake H, Lee JK, Hashimoto A, Masuyama K, Li J, Kuramoto Y, Higo S, Hikoso S, Hidaka K, Naito AT, Miyagawa S, Sawa Y, Komuro I, Sakata Y. |
| タイトル | Decreased YAP activity reduces proliferative ability in human induced pluripotent stem cell of duchenne muscular dystrophy derived cardiomyocytes. |
| ジャーナル | Sci Rep |
| Abstract |
Duchenne muscular dystrophy (DMD) is characterized by progressive muscle degeneration accompanied by dilated cardiomyopathy. Recently, abnormality of yes-associated protein (YAP) has been reported as the pathogenesis of muscle degeneration of DMD; however YAP activity remains unclear in dystrophic heart of DMD. Herein, we investigated YAP activity using disease-specific induced pluripotent stem cell (iPSC) derived cardiomyocytes (CMs) in DMD. DMD-iPSCs were generated from DMD patient with exon 48-54 deletion in DMD, and genome-edited (Ed)-DMD-iPSCs with in-frame (Ed-DMD-iPSCs) were created using CRISPR/Cas9. Nuclear translocation of YAP [nuclear (N)/cytoplasmic (C) ratio] was significantly lower in DMD-iPSC-CMs than in Ed-DMD-iPSC-CMs. In addition, Ki67 expression, indicating proliferative ability, was significantly lower in DMD-iPSC-CMs than Ed-DMD-iPSC-CMs. Therefore, immunofluorescent staining showed that actin stress fibers associated with YAP activity by mechanotransduction were disorganized in DMD-iPSC-CMs. Lysophosphatidic acid (LPA), a known lipid mediator on induction of actin polymerization, significantly increased YAP activity and actin dynamics in DMD-iPSC-CMs using live cell imaging. These results suggested that altered YAP activity due to impaired actin dynamics reduced proliferative ability in DMD-iPSC-CMs. Hence, decreased YAP activity in dystrophic heart may contribute to DMD-cardiomyopathy pathogenesis. |
| 巻・号 | 11(1) |
| ページ | 10351 |
| 公開日 | 2021-5-14 |
| DOI | 10.1038/s41598-021-89603-8 |
| PII | 10.1038/s41598-021-89603-8 |
| PMID | 33990626 |
| PMC | PMC8121946 |
| MeSH | Adaptor Proteins, Signal Transducing / deficiency* Adaptor Proteins, Signal Transducing / genetics Adult CRISPR-Cas Systems / genetics Cardiomyopathy, Dilated / genetics Cardiomyopathy, Dilated / pathology* Cell Proliferation Cells, Cultured Gene Editing Humans Induced Pluripotent Stem Cells / metabolism* Male Mechanotransduction, Cellular Muscular Dystrophy, Duchenne / complications* Muscular Dystrophy, Duchenne / genetics Muscular Dystrophy, Duchenne / pathology Myocytes, Cardiac / pathology* Primary Cell Culture Transcription Factors / deficiency* Transcription Factors / genetics YAP-Signaling Proteins |
| IF | 3.998 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 7 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | 201B7(HPS0063) |