2. Academic Validation
  3. Homeodomain-interacting protein kinase 2 regulates NLRP3 inflammasome activation through endoplasmic reticulum stress in septic liver injury

Homeodomain-interacting protein kinase 2 regulates NLRP3 inflammasome activation through endoplasmic reticulum stress in septic liver injury

  • J Int Med Res. 2023 May;51(5):3000605231173272. doi: 10.1177/03000605231173272.
Lijun Cao 1,  Min Wen 2,  Zhiqiang Hu 3,  Weihe Jia 4,  Jiayan Lin 1,  Bo Hu 1,  Gang Wu 1,  Shengchuang Tong 1,  Qinglin Chen 1,  Xingming Liu 5,  Xuhao Weng 6
Affiliations

Affiliations

  • 1 Department of Anesthesiology, No. 906 Hospital of the Chinese People's Liberation Army Joint Logistic Support Force, Ningbo, China.
  • 2 Department of Stomatology, No. 906 Hospital of the Chinese People's Liberation Army Joint Logistic Support Force, Ningbo, China.
  • 3 Department of Otorhinolaryngology, No. 906 Hospital of the Chinese People's Liberation Army Joint Logistic Support Force, Ningbo, China.
  • 4 Department of Nuclear Medicine, No. 906 Hospital of the Chinese People's Liberation Army Joint Logistic Support Force, Ningbo, China.
  • 5 Department of Urology, No. 906 Hospital of the Chinese People's Liberation Army Joint Logistic Support Force, Ningbo, China.
  • 6 Department of Burn and Plastic Surgery, No. 906 Hospital of the Chinese People's Liberation Army Joint Logistic Support Force, Ningbo, China.
PMID: 37190764 DOI: 10.1177/03000605231173272
Abstract

Objective: Septic liver injury is a major burden for the clinical management of sepsis. Hepatocyte cell death plays a crucial pathophysiological role in sepsis. A recent study proposed that NLRP3 inflammasome-mediated Pyroptosis participates in septic liver injury. Therefore, investigating the mechanism controlling this process may help manage sepsis.

Methods: We investigated the role of homeodomain-interacting protein kinase 2 (HIPK2) in regulating the NLRP3 inflammasome in vivo using mouse models and in vitro in primary hepatocytes.

Results: HIPK2 could improve liver injury and survival in a mouse model of sepsis. Overexpression of HIPK2 could suppress NLRP3 and caspase-1-p20 expression, while HIPK2 knockdown led to higher levels of these two molecules. Importantly, HIPK2 could suppress endoplasmic reticulum (ER) stress. Pharmacologically inhibiting ER stress could abolish activation of the NLRP3 inflammasome in hepatocytes with HIPK2 knockdown.

Conclusion: HIPK2 can regulate ER stress and NLRP3 inflammasome activation in the liver during sepsis, and HIPK2-mediated suppression of ER stress participates in regulating NLRP3 inflammasome activation. The present study highlights the role of HIPK2 in regulating the inflammasome in septic liver injury, which may serve as a target for managing sepsis.

Keywords

Homeodomain-interacting protein kinase 2; NLRP3; endoplasmic reticulum; inflammasome; liver injury; sepsis.

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