Overexpression of homeodomain-interacting protein kinase 2 (HIPK2) attenuates sepsis-mediated liver injury by restoring autophagy

Cell Death & Disease
Zhengyu JiangXiaoming Deng

Abstract

Sepsis is the leading cause of death in intensive care units worldwide. Autophagy has recently been shown to protect against sepsis-induced liver injury. Here, we investigated the roles of homeodomain-interacting protein kinase 2 (HIPK2) in the molecular mechanism of sepsis-induced liver injury. HIPK2 expression was reduced in sepsis-induced liver injury, and HIPK2 overexpression increased the survival rate and improved caecal ligation and puncture (CLP)-induced liver injury by reducing serum and liver aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) levels in mice with sepsis. HIPK2 overexpression significantly decreased CLP-induced release of inflammatory cytokines into the serum and attenuated oxidative stress-associated indicators in mice with CLP-induced liver injury, whereas HIPK2 knockdown produced the opposite results, suggesting that HIPK2 is a negative regulator of sepsis. Furthermore, HIPK2 overexpression inhibited lipopolysaccharide (LPS)-induced apoptosis of primary hepatocytes, increased the autophagic flux, and restored both autophagosome and autolysosome formation in the livers of CLP-induced mice by suppressing calpain signalling. Importantly, HIPK2 overexpression reduced...Continue Reading

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Citations

Oct 13, 2020·Frontiers in Cell and Developmental Biology·Francesca SardinaCinzia Rinaldo
Jun 25, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Jian ChenXiaogen Tao
Jul 11, 2021·Proceedings of the National Academy of Sciences of the United States of America·Fang ZhangBin Wei

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Methods Mentioned

BETA
ELISA
electrophoresis
flow cytometry
immunoprecipitation
ELISAs

Software Mentioned

ImageJ
SPSS

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