Exosomes derived from hucMSC attenuate renal fibrosis through CK1δ/β-TRCP-mediated YAP degradation

Exosomes from human umbilical cord mesenchymal stem cells (hucMSC-Ex) have been suggested as novel nanomaterials for regenerative medicine. Here we explored the roles of hucMSC-Ex through regulating Yes-associated protein (YAP) in renal injury repair by using rat unilateral ureteral obstruction (UUO...

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Autores principales: Ji, Cheng, Zhang, Jiahui, Zhu, Yuan, Shi, Hui, Yin, Siqi, Sun, Fengtian, Wang, Qiongni, Zhang, Leilei, Yan, Yongmin, Zhang, Xu, Xu, Wenrong, Qian, Hui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205986/
https://www.ncbi.nlm.nih.gov/pubmed/32382019
http://dx.doi.org/10.1038/s41419-020-2510-4
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author Ji, Cheng
Zhang, Jiahui
Zhu, Yuan
Shi, Hui
Yin, Siqi
Sun, Fengtian
Wang, Qiongni
Zhang, Leilei
Yan, Yongmin
Zhang, Xu
Xu, Wenrong
Qian, Hui
author_facet Ji, Cheng
Zhang, Jiahui
Zhu, Yuan
Shi, Hui
Yin, Siqi
Sun, Fengtian
Wang, Qiongni
Zhang, Leilei
Yan, Yongmin
Zhang, Xu
Xu, Wenrong
Qian, Hui
author_sort Ji, Cheng
collection PubMed
description Exosomes from human umbilical cord mesenchymal stem cells (hucMSC-Ex) have been suggested as novel nanomaterials for regenerative medicine. Here we explored the roles of hucMSC-Ex through regulating Yes-associated protein (YAP) in renal injury repair by using rat unilateral ureteral obstruction (UUO) models. Our study identified mechanical stress induced YAP nucleus expression and stimulated collagen deposition and interstitial fibrosis in the kidney. Then, infusion with hucMSC-Ex promoted YAP nuclear cytoplasmic shuttling and ameliorated renal fibrosis in UUO model. Interestingly, hucMSC-Ex delivered casein kinase 1δ (CK1δ) and E3 ubiquitin ligase β-TRCP to boost YAP ubiquitination and degradation. Knockdown of CK1δ and β-TRCP in hucMSC decreased the repairing effects of hucMSC-Ex on renal fibrosis. Our results suggest that hucMSC-Ex attenuates renal fibrosis through CK1δ/β-TRCP inhibited YAP activity, unveiling a new mechanism for the therapeutic effects of hucMSC-Ex on tissue injury and offering a potential approach for renal fibrosis treatment.
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spelling pubmed-72059862020-05-13 Exosomes derived from hucMSC attenuate renal fibrosis through CK1δ/β-TRCP-mediated YAP degradation Ji, Cheng Zhang, Jiahui Zhu, Yuan Shi, Hui Yin, Siqi Sun, Fengtian Wang, Qiongni Zhang, Leilei Yan, Yongmin Zhang, Xu Xu, Wenrong Qian, Hui Cell Death Dis Article Exosomes from human umbilical cord mesenchymal stem cells (hucMSC-Ex) have been suggested as novel nanomaterials for regenerative medicine. Here we explored the roles of hucMSC-Ex through regulating Yes-associated protein (YAP) in renal injury repair by using rat unilateral ureteral obstruction (UUO) models. Our study identified mechanical stress induced YAP nucleus expression and stimulated collagen deposition and interstitial fibrosis in the kidney. Then, infusion with hucMSC-Ex promoted YAP nuclear cytoplasmic shuttling and ameliorated renal fibrosis in UUO model. Interestingly, hucMSC-Ex delivered casein kinase 1δ (CK1δ) and E3 ubiquitin ligase β-TRCP to boost YAP ubiquitination and degradation. Knockdown of CK1δ and β-TRCP in hucMSC decreased the repairing effects of hucMSC-Ex on renal fibrosis. Our results suggest that hucMSC-Ex attenuates renal fibrosis through CK1δ/β-TRCP inhibited YAP activity, unveiling a new mechanism for the therapeutic effects of hucMSC-Ex on tissue injury and offering a potential approach for renal fibrosis treatment. Nature Publishing Group UK 2020-05-07 /pmc/articles/PMC7205986/ /pubmed/32382019 http://dx.doi.org/10.1038/s41419-020-2510-4 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Ji, Cheng
Zhang, Jiahui
Zhu, Yuan
Shi, Hui
Yin, Siqi
Sun, Fengtian
Wang, Qiongni
Zhang, Leilei
Yan, Yongmin
Zhang, Xu
Xu, Wenrong
Qian, Hui
Exosomes derived from hucMSC attenuate renal fibrosis through CK1δ/β-TRCP-mediated YAP degradation
title Exosomes derived from hucMSC attenuate renal fibrosis through CK1δ/β-TRCP-mediated YAP degradation
title_full Exosomes derived from hucMSC attenuate renal fibrosis through CK1δ/β-TRCP-mediated YAP degradation
title_fullStr Exosomes derived from hucMSC attenuate renal fibrosis through CK1δ/β-TRCP-mediated YAP degradation
title_full_unstemmed Exosomes derived from hucMSC attenuate renal fibrosis through CK1δ/β-TRCP-mediated YAP degradation
title_short Exosomes derived from hucMSC attenuate renal fibrosis through CK1δ/β-TRCP-mediated YAP degradation
title_sort exosomes derived from hucmsc attenuate renal fibrosis through ck1δ/β-trcp-mediated yap degradation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205986/
https://www.ncbi.nlm.nih.gov/pubmed/32382019
http://dx.doi.org/10.1038/s41419-020-2510-4
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