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Schistosoma japonicum egg antigen up-regulates fibrogenesis and inhibits proliferation in primary hepatic stellate cells in a concentration-dependent manner
  • ISSN号:1007-9327
  • 期刊名称:《世界胃肠病学杂志:英文版》
  • 分类:R532.2[医药卫生—临床医学;医药卫生—内科学]
  • 作者机构:[1]Institute of Liver Diseases,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology
  • 相关基金:Supported by Natural Science Foundation of China,No. 81071381
中文摘要:

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 e

英文摘要:

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.

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  • 《世界胃肠病学杂志:英文版》
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  • 国际标准刊号:ISSN:1007-9327
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