Cell Death and Disease (Dec 2022)

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

  • Xiaohua Lei,
  • Qiang Liu,
  • Wei Qin,
  • Qing Tong,
  • Zhenghao Li,
  • Wendi Xu,
  • Guoxing Liu,
  • Jie Fu,
  • Ju Zhang,
  • Tao Kuang,
  • Yaoli Shao,
  • Chun Liu,
  • Yu Fang,
  • Zhenyu Cao,
  • Likun Yan,
  • Zhiqiang Liu,
  • Siyuan Liu,
  • Hirofumi Yamamoto,
  • Masaki Mori,
  • Xin M. Liang,
  • Xundi Xu

DOI
https://doi.org/10.1038/s41419-022-05475-4
Journal volume & issue
Vol. 13, no. 12
pp. 1 – 10

Abstract

Read online

Abstract 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.