Pharmacological inhibition of mTOR attenuates replicative cell senescence and improves cellular function via regulating the STAT3-PIM1 axis in human cardiac progenitor cells.,Experimental & Molecular Medicine

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Pharmacological inhibition of mTOR attenuates replicative cell senescence and improves cellular function via regulating the STAT3-PIM1 axis in human cardiac progenitor cells.
Experimental & Molecular Medicine ( IF 9.5 ) Pub Date : 2020-04-09 , DOI: 10.1038/s12276-020-0374-4
Ji Hye Park _{1,

2,

3} , Na Kyoung Lee _{1,

2} , Hye Ji Lim _{1,

2} , Seung Taek Ji _{1,

2} , Yeon-Ju Kim _{1,

2} , Woong Bi Jang _{1,

2} , Da Yeon Kim _{1,

2} , Songhwa Kang _{1,

2} , Jisoo Yun _{1,

2} , Jong Seong Ha _{1,

2} , Hyungtae Kim ₄ , Dongjun Lee ₅ , Sang Hong Baek ₆ , Sang-Mo Kwon _{1,

4}

Affiliation

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.

中文翻译：

mTOR 的药理抑制可通过调节人心脏祖细胞中的 STAT3-PIM1 轴来减轻复制细胞衰老并改善细胞功能。

哺乳动物雷帕霉素靶蛋白（mTOR）信号通路有效调节细胞的能量状态并维持组织稳态。 mTOR 通路的失调与多种人类疾病有关。雷帕霉素是 mTOR 的特异性抑制剂，雷帕霉素对 mTOR 的药理学抑制可促进小鼠和人胚胎干细胞分化产生心肌细胞。这些研究强烈暗示了持续的 mTOR 活性在胚胎干细胞分化功能中的作用。然而，它们并没有直接解决人类心脏祖细胞中持续 mTOR 活性所需的效果。在本研究中，我们评估了雷帕霉素抑制 mTOR 对人心脏祖细胞的细胞功能的影响，发现雷帕霉素治疗显着减轻了人心脏祖细胞 (hCPC) 的复制细胞衰老并促进其细胞功能。此外，雷帕霉素不仅抑制 mTOR 信号传导，还影响 hCPC 中的信号通路，包括 STAT3 和 PIM1。因此，这些数据揭示了雷帕霉素在衰老 hCPC 中的关键功能，并提供了基于慢性 mTOR 活性的临床策略。

更新日期：2020-04-24

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