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Translationally controlled tumor protein promotes liver regeneration by activating mTORC2/AKT signaling

Zhibin Lin1, Xuan Zhang1, Jianlin Wang1

  • 1Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.

Cell Death & Disease
|January 25, 2020
PubMed

Insights

Translationally controlled tumor protein (TCTP) is crucial for liver regeneration (LR). TCTP knockdown impairs hepatocyte proliferation, lipid metabolism, and immune response during LR, highlighting its essential role in liver repair.

Area of Science:

  • Hepatology
  • Molecular Biology
  • Cellular Biology

Background:

  • Translationally controlled tumor protein (TCTP) is known for promoting cell proliferation and is implicated in growth and tumorigenesis.
  • The specific function and molecular mechanisms of TCTP in the context of liver regeneration (LR) remain largely unexplored.

Purpose of the Study:

  • To elucidate the role of TCTP in the process of liver regeneration.
  • To investigate the underlying molecular mechanisms by which TCTP influences liver repair.

Main Methods:

  • Generation of heterozygous TCTP mice to study TCTP's in vivo contribution.
  • Utilized TCTP-knockdown (KD) hepatic cell lines in a liver regeneration mimic model.
  • Analyzed hepatocyte proliferation, cell cycle markers, lipid metabolism, and immune responses.

Main Results:

  • TCTP knockdown significantly impaired liver regeneration in mice.
  • Hepatocyte proliferation was delayed, with disrupted cell cycle gene expression in TCTP-KD models.
  • TCTP deficiency led to degenerated lipid metabolism and abnormal immune responses during LR.
  • TCTP was found to activate the PI3K/AKT signaling pathway via mTORC2 regulation.
  • Elevated serum TCTP levels in humans correlated positively with liver enzyme recovery (ALT, AST) post-liver resection.

Conclusions:

  • This study provides the first evidence for the critical role of intracellular TCTP in liver regeneration.
  • TCTP is essential for maintaining normal hepatocyte proliferation, metabolic balance, and immune function during liver repair.
  • TCTP-mediated activation of PI3K/AKT signaling is a key mechanism underlying its function in LR.

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