NEK7 in chronic liver inflammatory and liver fibrosis
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    Abstract:

    Objective:This study aims to investigate the never in mitosis gene a-related kinase 7(NEK7)expression in liver fibrosis and its effect on nucleotide-binding oligomerization domain-like receptors(NLRP3)signal pathway to regulate liver fibrosis. Methods:HE staining,Masson staining and quantitative reverse transcription PCR(qRT-PCR)were used to evaluate those degree of hepatic fibrosis in normals and patients with cirrhosis. The expression of NEK7 in liver tissues of non-cirrhotic and cirrhotic patients was detected by Western blot and qRT-PCR. CD68-positive cells was determined by immunofluorescence tissue staining. To induce hepatic fibrosis,C57BL/6J mice were injected intraperitoneally with carbon tetrachloride(CCL4)twice a week for 8 weeks. C57BL/6J mice were injected through tail vein with macrophage-specific siRNA to knockdown the expression of NEK7 in macrophages. HE staining,Masson staining and sirius red staining were used to observe the changes of liver fibrosis in mice liver tissues. The level of the migration and aggregation of neutrophils and macrophages were monitored by immunohistochemistry tissue staining and immunofluorescence tissue staining. The impacts of NEK7 on NLRP3 signaling pathway were measured by Western blot. Results:In the fibrotic liver tissues,NEK7 expression was significantly higher than that in the normal tissues. Specific blockade of NEK7 in macrophages obviously attenuated liver fibrosis and hepatic inflammation in vivo. Specific blockade of NEK7 in macrophages also inhibited the activation of NLRP3 inflammasome signaling pathway. Conclusion:Inhibition of NEK7 may alleviate macrophage inflammation reaction and liver fibrosis through inhibiting NLRP3 inflammasome signaling pathway.

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王艺睿,王 皓,刘硕琛,倪 鸣,李相成. NEK7在慢性肝脏炎症及纤维化形成中的作用[J].南京医科大学学报(自然科学版英文版),2021,(5):663-669.

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  • Received:February 27,2021
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  • Online: June 02,2021
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