TRPM8 contributes to liver regeneration via mitochondrial energy metabolism mediated by PGC1α.

TRPM8 contributes to liver regeneration via mitochondrial energy metabolism mediated by PGC1α.
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DOI:
10.1038/s41419-022-05475-4
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发表时间:
2022-12-16
影响因子:
9
通讯作者:
Xu, Xundi
Xu, Xundi
中科院分区:
生物学1区
文献类型:
--
作者:
Lei, Xiaohua;Liu, Qiang;Qin, Wei;Tong, Qing;Li, Zhenghao;Xu, Wendi;Liu, Guoxing;Fu, Jie;Zhang, Ju;Kuang, Tao;Shao, Yaoli;Liu, Chun;Fang, Yu;Cao, Zhenyu;Yan, Likun;Liu, Zhiqiang;Liu, Siyuan;Yamamoto, Hirofumi;Mori, Masaki;Liang, Xinmin;Xu, Xundi

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肝再生障碍导致急性和慢性严重肝病的严重发病率。瞬时受体电位褪黑激素8(TRPM 8)参与多种过程,包括温度感应,离子稳态和细胞增殖。然而,TRPM8是否有助于肝再生仍不清楚。我们在体内和体外评估TRPM 8在肝再生和肝细胞增殖中的作用和机制。在这项研究中,我们发现TRPM8缺陷会损害小鼠的肝再生。从机制上讲,结果显示TRPM8敲除(KO)小鼠肝脏中的线粒体能量代谢减弱。此外,我们发现TRPM 8通过PGC1α促进肝细胞增殖。总之,这项研究表明TRPM8有助于肝切除术后小鼠的肝再生。调节TRPM8活性的遗传学方法和药理学方法可能有利于促进肝再生。
Impairment of liver regeneration leads to severe morbidity in acute and chronic severe liver disease. Transient receptor potential melastain 8 (TRPM8) is involved in a variety of processes, including temperature sensing, ion homeostasis, and cell proliferation. However, whether TRPM8 contributes to liver regeneration is still unclear. We assessed the effect and mechanism of TRPM8 in liver regeneration and hepatocyte proliferation in vivo and in vitro. In this study, we found that TRPM8 deficiency impairs liver regeneration in mice. Mechanistically, the results revealed that mitochondrial energy metabolism was attenuated in livers from TRPM8 knockout (KO) mice. Furthermore, we found that TRPM8 contributes to the proliferation of hepatocytes via PGC1α. Taken together, this study shows that TRPM8 contributes to liver regeneration in mice after hepatectomy. Genetic approaches and pharmacological approaches to regulate TRPM8 activity may be beneficial to the promotion of liver regeneration.
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