Targeted inhibition of NEK7 preventing sepsis-induced cardiomyopathy by inhibiting NLRP3 inflammasome

IF 4.8 2区医学 Q2 IMMUNOLOGY

International immunopharmacology Pub Date : 2025-02-26 DOI:10.1016/j.intimp.2025.114245

Lianghe Wen , Zhen Quan , Chunming Guan , Junbo Zheng , Yunlong Li , Siyao Zeng , Zheng Han , Ming Ye , Hongliang Wang

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引用次数: 0

Abstract

Background

Sepsis-induced cardiomyopathy (SIC) is a severe complication of sepsis; however, its pathogenesis remains elusive. This study aims to investigate the role of NMA-related kinase 7 (NEK7) in SIC.

Methods

C57BL/6 mice were stimulated with lipopolysaccharide (LPS) to assess NEK7 expression in the myocardium. AAV-shNEK7 was administered to improve cardiac function and survival rates. HL-1 cardiomyocytes were treated with si-NEK7 after LPS stimulation, and cell viability was measured. Molecular docking analysis and co-immunoprecipitation assays were used to validate the interaction between NEK7 and the NLRP3 inflammasome.

Results

NEK7 was significantly upregulated in the myocardium of LPS-stimulated C57BL/6 mice. Administration of AAV-shNEK7 improved cardiac function and enhanced survival rates. In LPS-stimulated HL-1 cardiomyocytes, si-NEK7 treatment increased cell viability compared to control cells, due to the suppression of pyroptosis through attenuation of NLRP3 inflammasome activation. Molecular docking analysis and co-immunoprecipitation assays confirmed that targeting NEK7 inhibits its interaction with NLRP3, thereby suppressing inflammasome activation and providing a protective effect.

Conclusions

NEK7 plays a crucial role in SIC by facilitating NLRP3 inflammasome activation. Targeting NEK7 presents a potential therapeutic approach for SIC.

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来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.