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toll-like receptor 5-mediated signaling enhances liver regeneration in mice

Military Medical Research 2021年第4期8卷 490-502页

作者： Wen Zhang Lei Wang Xue-Hua Sun Xian Liu Yang Xiao Jie Zhang Ting Wang Hui Chen Yi-Qun Zhan Miao Yu Chang-Hui Ge Chang-Yan Li Guang-Ming Ren Rong-Hua Yin Xiao-Ming Yang Department of Pharmaceutical Engineering School of Chemical Engineering and TechnologyTianjin UniversityTianjin 300072China. State Key Laboratory of Proteomics Beijing Proteome Research CenterNational Center for Protein Sciences(Beijing)Beijing Institute of LifeomicsBeijing 102206China. School of Basic Medical Sciences Anhui Medical UniversityHefei 230032Anhui ProvinceChina. Beijing Institute of Radiation Medicine Beijing 100850China.

Background:toll-like receptor 5(TLR5)-mediated pathways play critical roles in regulating the hepatic immune response and show hepatoprotective effects in mouse models of hepatic ***,the role of TLR5 in experimental models of liver regeneration has not been *** study aimed to investigate the role of TLR5 in partial hepatectomy(PHx)-induced liver ***:We performed 2/3 PHx in wild-type(WT)mice,TLR5 knockout mice,or TLR5 agonist CBLB502 treated mice,as a model of liver *** flagellin content was measured with ELISA,and hepatic TLR5 expression was determined with quantitative PCR analyses and flow *** study the effects of TLR5 on hepatocyte proliferation,we analyzed bromodeoxyuridine(BrdU)incorporation and proliferating cell nuclear antigen(PCNA)expression with immunohistochemistry(IHC)*** effects of TLR5 during the priming phase of liver regeneration were examined with quantitative PCR analyses of immediate early gene mRNA levels,and with Western blotting analysis of hepatic NF-κB and STAT3 *** and growth factor production after PHx were detected with real-time PCR and cytometric bead array(CBA)*** Red O staining and hepatic lipid concentrations were analyzed to examine the effect of TLR5 on hepatic lipid accumulation after ***:The bacterial flagellin content in the serum and liver increased,and the hepatic TLR5 expression was significantly up-regulated in WT mice after ***5-deficient mice exhibited diminished numbers of BrdU-and PCNA-positive cells,suppressed immediate early gene expression,and decreased cytokine and growth factor ***,PHx-induced hepatic NF-κB and STAT3 activation was inhibited in Tlr5–/–mice,as compared with WT ***,the administration of CBLB502 significantly promoted PHx-mediated hepatocyte proliferation,which was correlated with enhanced production of proinflammatory cytokines and the recruitment of macrophages

关键词： Liver regeneration Partial hepatectomy toll-like receptor 5 CBLB502 NF-κB

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