Next Article in Journal
ROS-Mediated Anti-Tumor Effect of Coptidis Rhizoma against Human Hepatocellular Carcinoma Hep3B Cells and Xenografts
Next Article in Special Issue
p16-3MR: A Novel Model to Study Cellular Senescence in Cigarette Smoke-Induced Lung Injuries
Previous Article in Journal
The Putative RNA-Binding Protein Dri1 Promotes the Loading of Kinesin-14/Klp2 to the Mitotic Spindle and Is Sequestered into Heat-Induced Protein Aggregates in Fission Yeast
Previous Article in Special Issue
Nicotinamide Phosphoribosyltransferase as a Key Molecule of the Aging/Senescence Process
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
IJMS
Volume 22
Issue 9
10.3390/ijms22094796
ijms-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
Correction published on 27 October 2022, see Int. J. Mol. Sci. 2022, 23(21), 13020.
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

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

by
Vinoth Kumar Rethineswaran
1,2,
Da Yeon Kim
1,2,3,
Yeon-Ju Kim
1,2,
WoongBi Jang
1,2,
Seung Taek Ji
1,2,
Le Thi Hong Van
1,2,
Ly Thanh Truong Giang
1,2,
Jong Seong Ha
1,2,
Jisoo Yun
1,2,
Jinsup Jung
4,* and
Sang-Mo Kwon
1,2,4,5,*
1
Convergence Stem Cell Research Center, Pusan National University, Yangsan 50612, Korea
2
Laboratory for Vascular Medicine and Stem Cell Biology, Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Korea
3
Korea Institute of Toxicology, Dajeon 34114, Korea
4
Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Korea
5
Research Institute of Convergence Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Korea
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(9), 4796; https://doi.org/10.3390/ijms22094796
Submission received: 19 April 2021 / Accepted: 27 April 2021 / Published: 30 April 2021 / Corrected: 27 October 2022
(This article belongs to the Special Issue Aging and Senescence)
Browse Figures
Versions Notes

Abstract

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.
Keywords: CHIR99021; GSK-3β; EPC; mTOR; lysosome; autophagy; senescence CHIR99021; GSK-3β; EPC; mTOR; lysosome; autophagy; senescence

Share and Cite

MDPI and ACS Style

Rethineswaran, V.K.; Kim, D.Y.; Kim, Y.-J.; Jang, W.; Ji, S.T.; Van, L.T.H.; Giang, L.T.T.; Ha, J.S.; Yun, J.; Jung, J.; et al. CHIR99021 Augmented the Function of Late Endothelial Progenitor Cells by Preventing Replicative Senescence. Int. J. Mol. Sci. 2021, 22, 4796. https://doi.org/10.3390/ijms22094796

AMA Style

Rethineswaran VK, Kim DY, Kim Y-J, Jang W, Ji ST, Van LTH, Giang LTT, Ha JS, Yun J, Jung J, et al. CHIR99021 Augmented the Function of Late Endothelial Progenitor Cells by Preventing Replicative Senescence. International Journal of Molecular Sciences. 2021; 22(9):4796. https://doi.org/10.3390/ijms22094796

Chicago/Turabian Style

Rethineswaran, Vinoth Kumar, Da Yeon Kim, Yeon-Ju Kim, WoongBi Jang, Seung Taek Ji, Le Thi Hong Van, Ly Thanh Truong Giang, Jong Seong Ha, Jisoo Yun, Jinsup Jung, and et al. 2021. "CHIR99021 Augmented the Function of Late Endothelial Progenitor Cells by Preventing Replicative Senescence" International Journal of Molecular Sciences 22, no. 9: 4796. https://doi.org/10.3390/ijms22094796

APA Style

Rethineswaran, V. K., Kim, D. Y., Kim, Y.-J., Jang, W., Ji, S. T., Van, L. T. H., Giang, L. T. T., Ha, J. S., Yun, J., Jung, J., & Kwon, S.-M. (2021). CHIR99021 Augmented the Function of Late Endothelial Progenitor Cells by Preventing Replicative Senescence. International Journal of Molecular Sciences, 22(9), 4796. https://doi.org/10.3390/ijms22094796

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop