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Mesenchymal stem cells ameliorate hyperglycemia-induced endothelial injury through modulation of mitophagy
Mitochondrial dysfunction and excessive mitochondrial reactive oxygen species (ROS) are fundamental contributors to endothelial injury in diabetic states. Mesenchymal stem cells (MSCs) have exhibited an extraordinary cytoprotective effect that extends to the modulation of mitochondrial homeostasis....
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6078996/ https://www.ncbi.nlm.nih.gov/pubmed/30082798 http://dx.doi.org/10.1038/s41419-018-0861-x |
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author | Zhu, Wuzheng Yuan, Yujia Liao, Guangneng Li, Lan Liu, Jingping Chen, Younan Zhang, Jie Cheng, Jingqiu Lu, Yanrong |
author_facet | Zhu, Wuzheng Yuan, Yujia Liao, Guangneng Li, Lan Liu, Jingping Chen, Younan Zhang, Jie Cheng, Jingqiu Lu, Yanrong |
author_sort | Zhu, Wuzheng |
collection | PubMed |
description | Mitochondrial dysfunction and excessive mitochondrial reactive oxygen species (ROS) are fundamental contributors to endothelial injury in diabetic states. Mesenchymal stem cells (MSCs) have exhibited an extraordinary cytoprotective effect that extends to the modulation of mitochondrial homeostasis. However, the underlying mechanisms have not been clearly defined. Emerging evidence has suggested that mitophagy could counteract mitochondrial-derived oxidative stress through the selective elimination of impaired or dysfunctional mitochondria. Therefore, we investigated whether MSCs could ameliorate high-glucose-induced endothelial injury through the modulation of mitophagy. We observed that exposure of human umbilical vein endothelial cells (HUVECs) to high glucose triggers mitochondrial impairment with excessive mitochondrial fragmentation and ROS generation, loss of membrane potential and reduced ATP production. Furthermore, mitophagy was blunted upon high glucose insult, which accelerated dysfunctional mitochondrial accumulation, initiating the mitochondrial apoptotic pathway and, eventually, endothelial dysfunction. MSCs treatment notably attenuated these perturbations accompanied by an enhancement of Pink1 and Parkin expression, whereas these beneficial effects of MSCs were abolished when either Pink1 or Parkin was knocked down. In aortas of diabetic rats, defective mitophagy was observed, which coincided with marked mitochondrial dysfunction. Ultrastructurally, RAECs from diabetic rats revealed a significant reduction in autophagic vacuoles and a marked increase in fragmented mitochondria. Importantly, the infusion of MSCs restored Pink1/Parkin-mediated mitophagy, ameliorated mitochondrial dysfunction and attenuated apoptosis in endothelial cells in diabetic rats. These results suggest that MSCs may protect endothelial cells from hyperglycemia-induced injury by ameliorating mitochondrial dysfunction via Pink1/Parkin –mediated mitophagy |
format | Online Article Text |
id | pubmed-6078996 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-60789962018-08-07 Mesenchymal stem cells ameliorate hyperglycemia-induced endothelial injury through modulation of mitophagy Zhu, Wuzheng Yuan, Yujia Liao, Guangneng Li, Lan Liu, Jingping Chen, Younan Zhang, Jie Cheng, Jingqiu Lu, Yanrong Cell Death Dis Article Mitochondrial dysfunction and excessive mitochondrial reactive oxygen species (ROS) are fundamental contributors to endothelial injury in diabetic states. Mesenchymal stem cells (MSCs) have exhibited an extraordinary cytoprotective effect that extends to the modulation of mitochondrial homeostasis. However, the underlying mechanisms have not been clearly defined. Emerging evidence has suggested that mitophagy could counteract mitochondrial-derived oxidative stress through the selective elimination of impaired or dysfunctional mitochondria. Therefore, we investigated whether MSCs could ameliorate high-glucose-induced endothelial injury through the modulation of mitophagy. We observed that exposure of human umbilical vein endothelial cells (HUVECs) to high glucose triggers mitochondrial impairment with excessive mitochondrial fragmentation and ROS generation, loss of membrane potential and reduced ATP production. Furthermore, mitophagy was blunted upon high glucose insult, which accelerated dysfunctional mitochondrial accumulation, initiating the mitochondrial apoptotic pathway and, eventually, endothelial dysfunction. MSCs treatment notably attenuated these perturbations accompanied by an enhancement of Pink1 and Parkin expression, whereas these beneficial effects of MSCs were abolished when either Pink1 or Parkin was knocked down. In aortas of diabetic rats, defective mitophagy was observed, which coincided with marked mitochondrial dysfunction. Ultrastructurally, RAECs from diabetic rats revealed a significant reduction in autophagic vacuoles and a marked increase in fragmented mitochondria. Importantly, the infusion of MSCs restored Pink1/Parkin-mediated mitophagy, ameliorated mitochondrial dysfunction and attenuated apoptosis in endothelial cells in diabetic rats. These results suggest that MSCs may protect endothelial cells from hyperglycemia-induced injury by ameliorating mitochondrial dysfunction via Pink1/Parkin –mediated mitophagy Nature Publishing Group UK 2018-08-06 /pmc/articles/PMC6078996/ /pubmed/30082798 http://dx.doi.org/10.1038/s41419-018-0861-x Text en © The Author(s) 2018 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 Zhu, Wuzheng Yuan, Yujia Liao, Guangneng Li, Lan Liu, Jingping Chen, Younan Zhang, Jie Cheng, Jingqiu Lu, Yanrong Mesenchymal stem cells ameliorate hyperglycemia-induced endothelial injury through modulation of mitophagy |
title | Mesenchymal stem cells ameliorate hyperglycemia-induced endothelial injury through modulation of mitophagy |
title_full | Mesenchymal stem cells ameliorate hyperglycemia-induced endothelial injury through modulation of mitophagy |
title_fullStr | Mesenchymal stem cells ameliorate hyperglycemia-induced endothelial injury through modulation of mitophagy |
title_full_unstemmed | Mesenchymal stem cells ameliorate hyperglycemia-induced endothelial injury through modulation of mitophagy |
title_short | Mesenchymal stem cells ameliorate hyperglycemia-induced endothelial injury through modulation of mitophagy |
title_sort | mesenchymal stem cells ameliorate hyperglycemia-induced endothelial injury through modulation of mitophagy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6078996/ https://www.ncbi.nlm.nih.gov/pubmed/30082798 http://dx.doi.org/10.1038/s41419-018-0861-x |
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