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

Cell Death Dis. 2022 Dec 16;13(12):1050. doi: 10.1038/s41419-022-05475-4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Energy Metabolism
  • Hepatectomy
  • Hepatocytes / metabolism
  • Liver / metabolism
  • Liver Regeneration* / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism
  • TRPM Cation Channels* / genetics
  • TRPM Cation Channels* / metabolism

Substances

  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • TRPM8 protein, mouse
  • TRPM Cation Channels