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

Autor:	Rethineswaran VK; Convergence Stem Cell Research Center, Pusan National University, Yangsan 50612, Korea.; Laboratory for Vascular Medicine and Stem Cell Biology, Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Korea., Kim DY; Convergence Stem Cell Research Center, Pusan National University, Yangsan 50612, Korea.; Laboratory for Vascular Medicine and Stem Cell Biology, Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Korea.; Korea Institute of Toxicology, Dajeon 34114, Korea., Kim YJ; Convergence Stem Cell Research Center, Pusan National University, Yangsan 50612, Korea.; Laboratory for Vascular Medicine and Stem Cell Biology, Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Korea., Jang W; Convergence Stem Cell Research Center, Pusan National University, Yangsan 50612, Korea.; Laboratory for Vascular Medicine and Stem Cell Biology, Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Korea., Ji ST; Convergence Stem Cell Research Center, Pusan National University, Yangsan 50612, Korea.; Laboratory for Vascular Medicine and Stem Cell Biology, Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Korea., Van LTH; Convergence Stem Cell Research Center, Pusan National University, Yangsan 50612, Korea.; Laboratory for Vascular Medicine and Stem Cell Biology, Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Korea., Giang LTT; Convergence Stem Cell Research Center, Pusan National University, Yangsan 50612, Korea.; Laboratory for Vascular Medicine and Stem Cell Biology, Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Korea., Ha JS; Convergence Stem Cell Research Center, Pusan National University, Yangsan 50612, Korea.; Laboratory for Vascular Medicine and Stem Cell Biology, Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Korea., Yun J; Convergence Stem Cell Research Center, Pusan National University, Yangsan 50612, Korea.; Laboratory for Vascular Medicine and Stem Cell Biology, Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Korea., Jung J; Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Korea., Kwon SM; Convergence Stem Cell Research Center, Pusan National University, Yangsan 50612, Korea.; Laboratory for Vascular Medicine and Stem Cell Biology, Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Korea.; Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Korea.; Research Institute of Convergence Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Korea.
Jazyk:	angličtina
Zdroj:	International journal of molecular sciences [Int J Mol Sci] 2021 Apr 30; Vol. 22 (9). Date of Electronic Publication: 2021 Apr 30.
DOI:	10.3390/ijms22094796
Abstrakt:	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.
Databáze:	MEDLINE
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