Objective To explore the biological function and mechanisms of LAMTOR2 during Klebsiella pneumoniae(K. pneumoniae) induced liver sepsis by establishing late endosomal/lysosomal adaptor 2(LAMTOR2) gene liver conditional knockout mouse model infected by K. pneumoniae. Methods LAMTOR2 gene liver conditional knockout mice (LAMTOR2; Alb-Cre) and littermate controls (LAMTOR2) were generated and bred. LAMTOR2 gene knockout efficiency in liver was determined by real-time quantitative PCR (RT-qPCR) and Western blot analysis. Then, both group mice were infected with K. pneumoniae, and survival rates and liver pathological changes were determined. The expression levels of liver TNF-α, IL-1β and CXCL1 mRNA were detected by RT-qPCR. Results LAMTOR2 gene liver conditional knockout mice were generated and bred successfully; compared to the littermate controls, LAMTOR2, Alb-Cre mice showed lower survival rates and more severe liver injury. The expression levels of TNF-α, IL-1β and CXCL1 mRNA were reduced in LAMTOR2 and the ability of immune response was decreased in mice. Alb-Cre mice liver compared to these of littermate controls post K. pneumoniae infections. Conclusion LAMTOR2 plays a protective role during K. pneumoniae-induced liver sepsis.
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Pharmacol Res
January 2025
Jena University Hospital, Department of Anesthesiology and Intensive Care Medicine, Friedrich-Schiller-University Jena, Jena, Germany; Jena University Hospital, Center for Sepsis Control and Care, Friedrich-Schiller-University Jena, Jena, Germany; Friedrich-Schiller-University Jena, Faculty of Medicine, Jena, Germany. Electronic address:
Sepsis is a life-threatening organ failure resulting from a poorly regulated infection response. Organ dysfunction includes hepatic involvement, weakening the immune system due to excretory liver failure, and metabolic dysfunction, increasing the death risk. Although experimental studies correlated excretory liver functionality with immune performance and survival rates in sepsis, the proteins and pathways involved remain unclear.
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Avtsyn Research Institute of Human Morphology, Petrovsky National Research Center of Surgery, Moscow, Russia.
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Department of Emergency, Wuhu Hospital, East China Normal University, the Second People's Hospital, Wuhu, China.
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Liver Transplant Unit, Gastrointestinal Surgical Center (GISC), Surgery Department, Mansoura University, Mansoura, Dakahleyya, Egypt.
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