[논문]Pharmacological inhibition of mTOR attenuates replicative cell senescence and improves cellular function via regulating the STAT3-PIM1 axis in human cardiac progenitor cells

Park, Ji Hye; Lee, Na Kyoung; Lim, Hye Ji; Ji, Seung taek; Kim, Yeon-Ju; Jang, Woong Bi; Kim, Da Yeon; Kang, Songhwa; Yun, Jisoo; Ha, Jong seong; Kim, Hyungtae; Lee, Dongjun; Baek, Sang Hong; Kwon, Sang-Mo

doi:10.1038/s12276-020-0374-4

[국내논문] Pharmacological inhibition of mTOR attenuates replicative cell senescence and improves cellular function via regulating the STAT3-PIM1 axis in human cardiac progenitor cells 원문보기

Experimental & molecular medicine : EMM, v.52 no.4, 2020년, pp.615 - 628

Park, Ji Hye (Laboratory of Regenerative Medicine and Stem Cell Biology, Department of Physiology, Medical Research Institute, School of Medicine, Pusan National University, Yangsan, 50612 Republic of Korea) , Lee, Na Kyoung (Laboratory of Regenerative Medicine and Stem Cell Biology, Department of Physiology, Medical Research Institute, School of Medicine, Pusan National University, Yangsan, 50612 Republic of Korea) , Lim, Hye Ji (Laboratory of Regenerative Medicine and Stem Cell Biology, Department of Physiology, Medical Research Institute, School of Medicine, Pusan National University, Yangsan, 50612 Republic of Korea) , Ji, Seung taek (Laboratory of Regenerative Medicine and Stem Cell Biology, Department of Physiology, Medical Research Institute, School of Medicine, Pusan National University, Yangsan, 50612 Republic of Korea) , Kim, Yeon-Ju (Laboratory of Regenerative Medicine and Stem Cell Biology, Department of Physiology, Medical Research Institute, School of Medicine, Pusan National University, Yangsan, 50612 Republic of Korea) , Jang, Woong Bi (Laboratory of Regenerativ) , Kim, Da Yeon , Kang, Songhwa , Yun, Jisoo , Ha, Jong seong , Kim, Hyungtae , Lee, Dongjun , Baek, Sang Hong , Kwon, Sang-Mo

Abstract ▼ AI-Helper

The mammalian target of rapamycin (mTOR) signaling pathway efficiently regulates the energy state of cells and maintains tissue homeostasis. Dysregulation of the mTOR pathway has been implicated in several human diseases. Rapamycin is a specific inhibitor of mTOR and pharmacological inhibition of mTOR with rapamycin promote cardiac cell generation from the differentiation of mouse and human embryonic stem cells. These studies strongly implicate a role of sustained mTOR activity in the differentiating functions of embryonic stem cells; however, they do not directly address the required effect for sustained mTOR activity in human cardiac progenitor cells. In the present study, we evaluated the effect of mTOR inhibition by rapamycin on the cellular function of human cardiac progenitor cells and discovered that treatment with rapamycin markedly attenuated replicative cell senescence in human cardiac progenitor cells (hCPCs) and promoted their cellular functions. Furthermore, rapamycin not only inhibited mTOR signaling but also influenced signaling pathways, including STAT3 and PIM1, in hCPCs. Therefore, these data reveal a crucial function for rapamycin in senescent hCPCs and provide clinical strategies based on chronic mTOR activity.Cardiac regeneration: preventing premature ageingDisrupting the mTOR signaling pathway, a major regulator of cell growth, protects human cardiac progenitor cells (hCPCs) from irreversible cell cycle arrest, also known as replicative cell senescence. Accumulation of senescent (aging) hCPCs leads to premature cardiac ageing and heart failure by hindering tissue repair in response to damage. Previous studies have shown that the mTOR inhibitor rapamycin promotes the differentiation of embryonic stem cells into hCPCs, but little is known about its effects on senescent hCPCs. Ji Hye Park at Pusan National University in South Korea and colleagues found that rapamycin reduced the expression of senescence-related markers in hCPCs and improved the ability of hCPCs to proliferate, migrate, and differentiate into cardiac muscle cells. These findings suggest that rapamycin could be used to aid cardiac regeneration following heart muscle damage caused by a heart attack.

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