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CHIR99021 Augmented the Function of Late Endothelial Progenitor Cells by Preventing Replicative Senescence

Endothelial progenitor cells (EPCs) are specialized cells in circulating blood, well known for their ability to form new vascular structures. Aging and various ailments such as diabetes, atherosclerosis and cardiovascular disease make EPCs vulnerable to decreasing in number, which affects their migr...

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Autores principales: Rethineswaran, Vinoth Kumar, Kim, Da Yeon, Kim, Yeon-Ju, Jang, WoongBi, Ji, Seung Taek, Van, Le Thi Hong, Giang, Ly Thanh Truong, Ha, Jong Seong, Yun, Jisoo, Jung, Jinsup, Kwon, Sang-Mo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124445/
https://www.ncbi.nlm.nih.gov/pubmed/33946516
http://dx.doi.org/10.3390/ijms22094796
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author Rethineswaran, Vinoth Kumar
Kim, Da Yeon
Kim, Yeon-Ju
Jang, WoongBi
Ji, Seung Taek
Van, Le Thi Hong
Giang, Ly Thanh Truong
Ha, Jong Seong
Yun, Jisoo
Jung, Jinsup
Kwon, Sang-Mo
author_facet Rethineswaran, Vinoth Kumar
Kim, Da Yeon
Kim, Yeon-Ju
Jang, WoongBi
Ji, Seung Taek
Van, Le Thi Hong
Giang, Ly Thanh Truong
Ha, Jong Seong
Yun, Jisoo
Jung, Jinsup
Kwon, Sang-Mo
author_sort Rethineswaran, Vinoth Kumar
collection PubMed
description Endothelial progenitor cells (EPCs) are specialized cells in circulating blood, well known for their ability to form new vascular structures. Aging and various ailments such as diabetes, atherosclerosis and cardiovascular disease make EPCs vulnerable to decreasing in number, which affects their migration, proliferation and angiogenesis. Myocardial ischemia is also linked to a reduced number of EPCs and their endothelial functional role, which hinders proper blood circulation to the myocardium. The current study shows that an aminopyrimidine derivative compound (CHIR99021) induces the inhibition of GSK-3β in cultured late EPCs. GSK-3β inhibition subsequently inhibits mTOR by blocking the phosphorylation of TSC2 and lysosomal localization of mTOR. Furthermore, suppression of GSK-3β activity considerably increased lysosomal activation and autophagy. The activation of lysosomes and autophagy by GSK-3β inhibition not only prevented replicative senescence of the late EPCs but also directed their migration, proliferation and angiogenesis. To conclude, our results demonstrate that lysosome activation and autophagy play a crucial role in blocking the replicative senescence of EPCs and in increasing their endothelial function. Thus, the findings provide an insight towards the treatment of ischemia-associated cardiovascular diseases based on the role of late EPCs.
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spelling pubmed-81244452021-05-17 CHIR99021 Augmented the Function of Late Endothelial Progenitor Cells by Preventing Replicative Senescence Rethineswaran, Vinoth Kumar Kim, Da Yeon Kim, Yeon-Ju Jang, WoongBi Ji, Seung Taek Van, Le Thi Hong Giang, Ly Thanh Truong Ha, Jong Seong Yun, Jisoo Jung, Jinsup Kwon, Sang-Mo Int J Mol Sci Article Endothelial progenitor cells (EPCs) are specialized cells in circulating blood, well known for their ability to form new vascular structures. Aging and various ailments such as diabetes, atherosclerosis and cardiovascular disease make EPCs vulnerable to decreasing in number, which affects their migration, proliferation and angiogenesis. Myocardial ischemia is also linked to a reduced number of EPCs and their endothelial functional role, which hinders proper blood circulation to the myocardium. The current study shows that an aminopyrimidine derivative compound (CHIR99021) induces the inhibition of GSK-3β in cultured late EPCs. GSK-3β inhibition subsequently inhibits mTOR by blocking the phosphorylation of TSC2 and lysosomal localization of mTOR. Furthermore, suppression of GSK-3β activity considerably increased lysosomal activation and autophagy. The activation of lysosomes and autophagy by GSK-3β inhibition not only prevented replicative senescence of the late EPCs but also directed their migration, proliferation and angiogenesis. To conclude, our results demonstrate that lysosome activation and autophagy play a crucial role in blocking the replicative senescence of EPCs and in increasing their endothelial function. Thus, the findings provide an insight towards the treatment of ischemia-associated cardiovascular diseases based on the role of late EPCs. MDPI 2021-04-30 /pmc/articles/PMC8124445/ /pubmed/33946516 http://dx.doi.org/10.3390/ijms22094796 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rethineswaran, Vinoth Kumar
Kim, Da Yeon
Kim, Yeon-Ju
Jang, WoongBi
Ji, Seung Taek
Van, Le Thi Hong
Giang, Ly Thanh Truong
Ha, Jong Seong
Yun, Jisoo
Jung, Jinsup
Kwon, Sang-Mo
CHIR99021 Augmented the Function of Late Endothelial Progenitor Cells by Preventing Replicative Senescence
title CHIR99021 Augmented the Function of Late Endothelial Progenitor Cells by Preventing Replicative Senescence
title_full CHIR99021 Augmented the Function of Late Endothelial Progenitor Cells by Preventing Replicative Senescence
title_fullStr CHIR99021 Augmented the Function of Late Endothelial Progenitor Cells by Preventing Replicative Senescence
title_full_unstemmed CHIR99021 Augmented the Function of Late Endothelial Progenitor Cells by Preventing Replicative Senescence
title_short CHIR99021 Augmented the Function of Late Endothelial Progenitor Cells by Preventing Replicative Senescence
title_sort chir99021 augmented the function of late endothelial progenitor cells by preventing replicative senescence
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124445/
https://www.ncbi.nlm.nih.gov/pubmed/33946516
http://dx.doi.org/10.3390/ijms22094796
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