硫化氢通过上调 SIRT1 信号通路促进出生后心肌细胞增殖

IF 1.2 4区 医学 Q3 CARDIAC & CARDIOVASCULAR SYSTEMS
Lu Gan, Peng Cheng, Jieyun Wu, Qiyong Li, Jigang Pan, Yan Ding, Xiufeng Gao, Li Chen
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引用次数: 0

摘要

硫化氢(H2S)已被确认为一种新型的气体递质和一种重要的抗氧化剂,可激活各种细胞靶点,调节哺乳动物的生理和病理过程。然而,在生理条件下,它是否参与调节小鼠出生后发育过程中心肌细胞(CM)的增殖仍不清楚。本研究的主要目的是评估 H2S 在小鼠出生后 CM 增殖中的作用及其调控分子机制。我们发现,硫氢化钠(NaHS,最广泛使用的 H2S 供体,50-200 μM)能以剂量依赖的方式在体外增加新生小鼠原代 CM 的增殖。同样,外源性给予 H2S 也能促进 CM 增殖,并增加出生后 7 天和 14 天体内 CM 的总数。此外,我们还观察到 NaHS 处理后 SIRT1 蛋白表达明显上调。用 EX-527 或 si-SIRT1 抑制 SIRT1 会减少 CM 的增殖,而用 SRT1720 增强 SIRT1 的活化会促进 CM 的增殖。同时,药物和基因阻断 SIRT1 可抑制 NaHS 对 CM 增殖的影响。综上所述,这些结果揭示了H2S在体内和体外对CM的增殖起促进作用,而SIRT1是H2S介导的CM增殖所必需的,这表明H2S可能是出生后时间窗心脏发育的潜在调节因子。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Hydrogen Sulfide Promotes Postnatal Cardiomyocyte Proliferation by Upregulating SIRT1 Signaling Pathway

Hydrogen sulfide (H2S) has been identified as a novel gasotransmitter and a substantial antioxidant that can activate various cellular targets to regulate physiological and pathological processes in mammals. However, under physiological conditions, it remains unclear whether it is involved in regulating cardiomyocyte (CM) proliferation during postnatal development in mice. This study mainly aimed to evaluate the role of H2S in postnatal CM proliferation and its regulating molecular mechanisms. We found that sodium hydrosulfide (NaHS, the most widely used H2S donor, 50-200 μM) increased neonatal mouse primary CM proliferation in a dose-dependent manner in vitro. Consistently, exogenous administration of H2S also promoted CM proliferation and increased the total number of CMs at postnatal 7 and 14 days in vivo. Moreover, we observed that the protein expression of SIRT1 was significantly upregulated after NaHS treatment. Inhibition of SIRT1 with EX-527 or si-SIRT1 decreased CM proliferation, while enhancement of the activation of SIRT1 with SRT1720 promoted CM proliferation. Meanwhile, pharmacological and genetic blocking of SIRT1 repressed the effect of NaHS on CM proliferation. Taken together, these results reveal that H2S plays a promotional role in proliferation of CMs in vivo and in vitro and SIRT1 is required for H2S-mediated CM proliferation, which indicates that H2S may be a potential modulator for heart development in postnatal time window.

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来源期刊
International heart journal
International heart journal 医学-心血管系统
CiteScore
2.50
自引率
6.70%
发文量
148
审稿时长
6-12 weeks
期刊介绍: Authors of research articles should disclose at the time of submission any financial arrangement they may have with a company whose product figures prominently in the submitted manuscript or with a company making a competing product. Such information will be held in confidence while the paper is under review and will not influence the editorial decision, but if the article is accepted for publication, the editors will usually discuss with the authors the manner in which such information is to be communicated to the reader.
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