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Reversing metabolic reprogramming by CPT1 inhibition with etomoxir promotes cardiomyocyte proliferation and heart regeneration via DUSP1 ADP-ribosylation-mediated p38 MAPK phosphorylation 期刊论文 WOS高被引论文

编号：

3EC5ACEDEFDD4D1D35E5C38B1B8DA3BE
作者：

Tang, Luxun#^[1,2,3]Shi, Yu#^[1,2]Liao, Qiao#^[1,2]Wang, Feng^[1,2];Wu, Hao^[1,2];Ren, Hongmei^[1,2];Wang, Xuemei^[1,2];Fu, Wenbin^[1,2];Shou, Jialing^[1,2];Wang, Wei Eric^[1,2];Jose, Pedro A.^[4];Yang, Yongjian*^[3]Zeng, Chunyu(曾春雨)*^[1,2,5,6,7]
语种：

英文
期刊：

ACTA PHARMACEUTICA SINICA B ISSN：2211-3835 2025 年 15 卷 1 期 (256 - 277) ; JAN
收录：
关键词：

Metabolic reprogramming Cardiomyocyte proliferation Carnitine palmitoyltransferase 1 Etomoxir Fatty acid oxidation Glycolysis ADP-ribosylation p38 MAPK
摘要：

The neonatal mammalian heart has a remarkable regenerative capacity, while the adult heart has difficulty to regenerate. A metabolic reprogramming from glycolysis to fatty acid oxidation occurs along with the loss of cardiomyocyte proliferative capacity shortly after birth. In this study, we sought to determine if and how metabolic reprogramming regulates cardiomyocyte proliferation. Reversing metabolic reprogramming by carnitine palmitoyltransferase 1 (CPT1) inhibition, using cardiac-specific Cpt1 a and Cpt1 b knockout mice promoted cardiomyocyte proliferation and improved cardiac function post-myocardial infarction. The inhibition of CPT1 is of pharmacological significance because those protective effects were replicated by etomoxir, a CPT1 inhibitor. CPT1 inhibition, by decreasing poly(ADP-ribose) polymerase 1 expression, reduced ADP-ribosylation of dual-specificity phosphatase 1 in cardiomyocytes, leading to decreased p38 MAPK phosphorylation, and stimulation of cardiomyocyte proliferation. Our present study indicates that reversing metabolic reprogramming is an effective strategy to stimulate adult cardiomyocyte proliferation. CPT1 is a potential therapeutic target for promoting heart regeneration and myocardial infarction treatment. 2025 The Authors. Published by Elsevier B.V. on behalf of Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
推荐引用方式
GB/T 7714：

Tang Luxun,Shi Yu,Liao Qiao, et al. Reversing metabolic reprogramming by CPT1 inhibition with etomoxir promotes cardiomyocyte proliferation and heart regeneration via DUSP1 ADP-ribosylation-mediated p38 MAPK phosphorylation [J].ACTA PHARMACEUTICA SINICA B,2025,15(1):256-277.
APA：

Tang Luxun,Shi Yu,Liao Qiao,Wang Feng,&Zeng Chunyu.(2025).Reversing metabolic reprogramming by CPT1 inhibition with etomoxir promotes cardiomyocyte proliferation and heart regeneration via DUSP1 ADP-ribosylation-mediated p38 MAPK phosphorylation .ACTA PHARMACEUTICA SINICA B,15(1):256-277.
MLA：

Tang Luxun, et al. "Reversing metabolic reprogramming by CPT1 inhibition with etomoxir promotes cardiomyocyte proliferation and heart regeneration via DUSP1 ADP-ribosylation-mediated p38 MAPK phosphorylation" .ACTA PHARMACEUTICA SINICA B 15,1(2025):256-277.
入库时间：

2025/7/3 21:46:05
更新时间：

2025/7/21 3:06:53

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