Unknown

Dataset Information

0

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


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 the elevated cytosolic Ca2+ concentration in LPS-treated primary hepatocytes by interacting with calpain 1 and calmodulin. Finally, several anti-inflammatory drugs, including resveratrol, aspirin, vitamin E and ursolic acid, significantly increased the levels of the HIPK2 mRNA and protein by modulating promoter activity and the 3'-UTR stability of the HIPK2 gene. In conclusion, HIPK2 overexpression may improve sepsis-induced liver injury by restoring autophagy and thus might be a promising target for the clinical treatment of sepsis.

SUBMITTER: Jiang Z 

PROVIDER: S-EPMC6113252 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Jiang Zhengyu Z   Bo Lulong L   Meng Yan Y   Wang Chen C   Chen Tianxing T   Wang Changli C   Yu Xiya X   Deng Xiaoming X  

Cell death & disease 20180828 9


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 an  ...[more]

Similar Datasets

| S-EPMC5341236 | biostudies-literature
| S-EPMC3933419 | biostudies-literature
| S-EPMC7138288 | biostudies-literature
| S-EPMC5875702 | biostudies-literature
| S-EPMC7349807 | biostudies-literature
| S-EPMC5186405 | biostudies-literature
| S-EPMC7062965 | biostudies-literature
| S-EPMC8892593 | biostudies-literature
| S-EPMC4949129 | biostudies-literature
| S-EPMC5101611 | biostudies-other