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Updated: Nov 2, 2025

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
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TNFAIP3 Interacting Protein 3 Is an Activator of Hippo-YAP Signaling Protecting Against Hepatic Ischemia/Reperfusion

Junjie Zhou1,2, Manli Hu1,2, Meiling He1,2

  • 1Medical Science Research Center, Zhongnan Hospital, School of Basic Medical Sciences, Wuhan University, Wuhan, China.

Hepatology (Baltimore, Md.)
|June 16, 2021
PubMed
Abstract

Insights

Tumor necrosis factor alpha-induced protein 3-interacting protein 3 (TNIP3) protects against liver injury following ischemia/reperfusion (I/R) by activating the Hippo-YAP pathway. Upregulating TNIP3 may improve outcomes for liver surgery patients.

Area of Science:

  • Hepatology
  • Molecular Biology
  • Surgical Research

Background:

  • Hepatic ischemia/reperfusion (I/R) injury is a major cause of graft failure and rejection after liver surgery.
  • Identifying key regulators of hepatic I/R injury is crucial for improving surgical outcomes.
  • Tumor necrosis factor alpha-induced protein 3-interacting protein 3 (TNIP3) is investigated for its role in hepatic I/R injury.

Purpose of the Study:

  • To determine the role of TNIP3 in hepatic I/R injury.
  • To elucidate the underlying mechanisms of TNIP3's action in the liver.
  • To assess TNIP3 as a potential therapeutic target for liver surgery.

Main Methods:

  • Assessed TNIP3 expression in human and mouse livers subjected to I/R.
  • Utilized hepatocyte-specific Tnip3 overexpression and ablation models in mice.
  • Investigated the interaction of TNIP3 with LATS2 and its effect on YAP signaling.
  • Employed adeno-associated virus (AAV) for in vivo TNIP3 delivery.

Main Results:

  • TNIP3 expression was significantly upregulated in I/R-affected livers.
  • TNIP3 overexpression attenuated liver necrosis and inflammation, while ablation aggravated injury.
  • TNIP3 activated the Hippo-YAP pathway by promoting LATS2 ubiquitination and decreasing YAP phosphorylation.
  • AAV-mediated TNIP3 delivery protected against hepatic I/R injury in mice.

Conclusions:

  • TNIP3 mitigates hepatic I/R injury by activating the Hippo-YAP pathway.
  • TNIP3 facilitates LATS2 degradation, leading to YAP activation.
  • TNIP3 is a promising therapeutic target for improving liver surgery prognosis.

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