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PSME4 determines mesenchymal stem cell fate towards cardiac commitment through YAP1 degradation
The regeneration of myocardium following acute circulatory events remains a challenge, despite numerous efforts. Mesenchymal stem cells (MSCs) present a promising cell therapy option, but their differentiation into cardiomyocytes is a time-consuming process. Although it has been demonstrated that PS...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Korean Physiological Society and The Korean Society of Pharmacology
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10316190/ https://www.ncbi.nlm.nih.gov/pubmed/37386838 http://dx.doi.org/10.4196/kjpp.2023.27.4.407 |
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author | Kim, Mira Kim, Yong Sook Ahn, Youngkeun Eom, Gwang Hyeon Yoon, Somy |
author_facet | Kim, Mira Kim, Yong Sook Ahn, Youngkeun Eom, Gwang Hyeon Yoon, Somy |
author_sort | Kim, Mira |
collection | PubMed |
description | The regeneration of myocardium following acute circulatory events remains a challenge, despite numerous efforts. Mesenchymal stem cells (MSCs) present a promising cell therapy option, but their differentiation into cardiomyocytes is a time-consuming process. Although it has been demonstrated that PSME4 degrades acetyl-YAP1, the role of PSME4 in the cardiac commitment of MSCs has not been fully elucidated. Here we reported the novel role of PSME4 in MSCs cardiac commitment. It was found that overnight treatment with apicidin in primary-cultured mouse MSCs led to rapid cardiac commitment, while MSCs from PSME4 knock-out mice did not undergo this process. Cardiac commitment was also observed using lentivirus-mediated PSME4 knockdown in immortalized human MSCs. Immunofluorescence and Western blot experiments revealed that YAP1 persisted in the nucleus of PSME4 knockdown cells even after apicidin treatment. To investigate the importance of YAP1 removal, MSCs were treated with shYAP1 and apicidin simultaneously. This combined treatment resulted in rapid YAP1 elimination and accelerated cardiac commitment. However, overexpression of acetylation-resistant YAP1 in apicidin-treated MSCs impeded cardiac commitment. In addition to apicidin, the universal effect of histone deacetylase (HDAC) inhibition on cardiac commitment was confirmed using tubastatin A and HDAC6 siRNA. Collectively, this study demonstrates that PSME4 is crucial for promoting the cardiac commitment of MSCs. HDAC inhibition acetylates YAP1 and facilitates its translocation to the nucleus, where it is removed by PSME4, promoting cardiac commitment. The failure of YAP1 to translocate or be eliminated from the nucleus results in the MSCs' inability to undergo cardiac commitment. |
format | Online Article Text |
id | pubmed-10316190 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | The Korean Physiological Society and The Korean Society of Pharmacology |
record_format | MEDLINE/PubMed |
spelling | pubmed-103161902023-07-04 PSME4 determines mesenchymal stem cell fate towards cardiac commitment through YAP1 degradation Kim, Mira Kim, Yong Sook Ahn, Youngkeun Eom, Gwang Hyeon Yoon, Somy Korean J Physiol Pharmacol Original Article The regeneration of myocardium following acute circulatory events remains a challenge, despite numerous efforts. Mesenchymal stem cells (MSCs) present a promising cell therapy option, but their differentiation into cardiomyocytes is a time-consuming process. Although it has been demonstrated that PSME4 degrades acetyl-YAP1, the role of PSME4 in the cardiac commitment of MSCs has not been fully elucidated. Here we reported the novel role of PSME4 in MSCs cardiac commitment. It was found that overnight treatment with apicidin in primary-cultured mouse MSCs led to rapid cardiac commitment, while MSCs from PSME4 knock-out mice did not undergo this process. Cardiac commitment was also observed using lentivirus-mediated PSME4 knockdown in immortalized human MSCs. Immunofluorescence and Western blot experiments revealed that YAP1 persisted in the nucleus of PSME4 knockdown cells even after apicidin treatment. To investigate the importance of YAP1 removal, MSCs were treated with shYAP1 and apicidin simultaneously. This combined treatment resulted in rapid YAP1 elimination and accelerated cardiac commitment. However, overexpression of acetylation-resistant YAP1 in apicidin-treated MSCs impeded cardiac commitment. In addition to apicidin, the universal effect of histone deacetylase (HDAC) inhibition on cardiac commitment was confirmed using tubastatin A and HDAC6 siRNA. Collectively, this study demonstrates that PSME4 is crucial for promoting the cardiac commitment of MSCs. HDAC inhibition acetylates YAP1 and facilitates its translocation to the nucleus, where it is removed by PSME4, promoting cardiac commitment. The failure of YAP1 to translocate or be eliminated from the nucleus results in the MSCs' inability to undergo cardiac commitment. The Korean Physiological Society and The Korean Society of Pharmacology 2023-07-01 2023-07-01 /pmc/articles/PMC10316190/ /pubmed/37386838 http://dx.doi.org/10.4196/kjpp.2023.27.4.407 Text en Copyright © Korean J Physiol Pharmacol https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0 (https://creativecommons.org/licenses/by-nc/4.0/) ) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Kim, Mira Kim, Yong Sook Ahn, Youngkeun Eom, Gwang Hyeon Yoon, Somy PSME4 determines mesenchymal stem cell fate towards cardiac commitment through YAP1 degradation |
title | PSME4 determines mesenchymal stem cell fate towards cardiac commitment through YAP1 degradation |
title_full | PSME4 determines mesenchymal stem cell fate towards cardiac commitment through YAP1 degradation |
title_fullStr | PSME4 determines mesenchymal stem cell fate towards cardiac commitment through YAP1 degradation |
title_full_unstemmed | PSME4 determines mesenchymal stem cell fate towards cardiac commitment through YAP1 degradation |
title_short | PSME4 determines mesenchymal stem cell fate towards cardiac commitment through YAP1 degradation |
title_sort | psme4 determines mesenchymal stem cell fate towards cardiac commitment through yap1 degradation |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10316190/ https://www.ncbi.nlm.nih.gov/pubmed/37386838 http://dx.doi.org/10.4196/kjpp.2023.27.4.407 |
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