Schistosoma japonicum egg antigen up-regulates fibrogenesis and inhibits proliferation in primary hepatic stellate cells in a concentration-dependent manner  

作　　者：Ping Liu Mi Wang Xiao-Dan Lu Shu-Juan Zhang Wang-Xian Tang 

机构地区：[1]Institute of Liver Diseases,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology

出　　处：《World Journal of Gastroenterology》2013年第8期1230-1238,共9页世界胃肠病学杂志（英文版）

基　　金：Supported by Natural Science Foundation of China,No. 81071381

摘　　要：AIM:To investigate the effects of different concentrations of Schistosoma japonicum(S.japonicum) egg antigen on fibrogenesis and apoptosis in primary hepatic stellate cells(HSCs).METHODS:A mouse model of schistosomiasis-associated liver fibrosis(SSLF) was established by infecting mice with schistosomal cercaria via the abdomen.HSCs were isolated from SSLF mice by discontinuous density gradient centrifugation,and their identity was confirmed by immunofluorescence double staining of α-smooth muscle actin(α-SMA) and desmin.The growth inhibitory effect and 50% inhibitory concentration(IC50) of S.japonicum egg antigen for primary HSCs(24 h) were determined using a cell counting kit-8(CCK-8) assay.The expression levels of α-SMA,matrix metalloproteinase-9(MMOL/LP-9) and tissue inhibitor of metalloproteinases-1(TIMP-1) in HSCs in response to different concentrations of S.japonicum egg antigen were detected by Western blotting and real-time reverse transcription-polymerase chain reaction.The levels of phospho-P38(P-P38),phospho-Jun N-terminal kinase(P-JNK) and phospho-Akt(P-AKT) in HSCs were detected by Western blotting.RESULTS:An SSLF mouse model was established,and primary HSCs were successfully isolated and cultured.S.japonicum egg antigen inhibited HSC proliferation in a concentration-dependent manner.The IC50 of the S.japonicum egg antigen was 244.53 ± 35.26 μg/mL.S.japonicum egg antigen enhanced α-SMA expression at both the mRNA and protein levels and enhanced TIMP-1 expression at the mRNA level in HSCs(P < 0.05),whereas the expression of MMOL/LP-9 was attenuated at both the mRNA and protein levels in a concentration-dependent manner(P < 0.05).A high concentration of S.japonicum egg antigen enhanced P-P38,P-JNK and P-AKT activation(P < 0.05).The changes in α-SMA and MMOL/LP-9 expression induced by S.japonicum egg antigen were closely correlated with P-P38 and P-JNK activation(P < 0.05).The attenuation of MMOL/LP-9 was also correlated with P-AKT activation(P < 0.05),but the increase in α-SMA expression was noAIM: To investigate the effects of different concentrations of Schistosoma japonicum (S. japonicum) egg antigen on fibrogenesis and apoptosis in primary hepatic stellate cells (HSCs). METHODS: A mouse model of schistosomiasis-associated liver fibrosis (SSLF) was established by infecting mice with schistosomal cercaria via the abdomen. HSCs were isolated from SSLF mice by discontinuous density gradient centrifugation, and their identity was confirmed by immunofluorescence double staining of α-smooth muscle actin (α-SMA) and desmin. The growth inhibitory effect and 50% inhibitory concentration (IC50) of S. japonicum egg antigen for primary HSCs (24 h) were determined using a cell counting kit-8 (CCK-8) assay. The expression levels of α-SMA, matrix metalloproteinase-9 (MMOL/LP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1) in HSCs in response to different concentrations of S. japonicum egg antigen were detected by Western blotting and real-time reverse transcription-polymerase chain reaction. The levels of phospho-P38 (P-P38), phospho-Jun N-terminal kinase (P-JNK) and phospho-Akt (P-AKT) in HSCs were detected by Western blotting. RESULTS: An SSLF mouse model was established, and primary HSCs were successfully isolated and cultured. S. japonicum egg antigen inhibited HSC proliferation in a concentration-dependent manner. The IC50 of the S. japonicum egg antigen was 244.53 ± 35.26 μg/mL. S. japonicum egg antigen enhanced α-SMA expression at both the mRNA and protein levels and enhanced TIMP-1 expression at the mRNA level in HSCs (P < 0.05), whereas the expression of MMOL/LP-9 was attenuated at both the mRNA and protein levels in a concentration-dependent manner (P < 0.05). A high concentration of S. japonicum egg antigen enhanced P-P38, P-JNK and P-AKT activation (P < 0.05). The changes in α-SMA and MMOL/LP-9 expression induced by S. japonicum egg antigen were closely correlated with P-P38 and P-JNK activation (P < 0.05). The attenuation of MMOL/LP-9 was also correlated with P-AKT activation (P < 0.

关 键 词：SCHISTOSOMIASIS Liver FIBROSIS Hepatic stellate cells MITOGEN-ACTIVATED protein KINASE Akt 

分 类 号：R532.2[医药卫生—内科学]