运用Western-blot技术和免疫组织化学来检测丝裂原活化蛋白激酶(mitogen-activated protein kinases,MAPKs)家族成员细胞外调节蛋白激酶(extracellular regulated protein kinase,ERK)和c-Jun氨基末端激酶(c-Jun N-terminal kinase,JNK...运用Western-blot技术和免疫组织化学来检测丝裂原活化蛋白激酶(mitogen-activated protein kinases,MAPKs)家族成员细胞外调节蛋白激酶(extracellular regulated protein kinase,ERK)和c-Jun氨基末端激酶(c-Jun N-terminal kinase,JNK)在不同生殖特性鲫鲤杂交鱼性腺组织中的表达。研究表明,JNK、ERK在鱼类性腺组织中均有较高量的表达,但在鱼类卵巢和精巢间、雌核发育二倍体鲫鲤和不同倍性鱼的性腺组织间,JNK或ERK的表达量并不存在明显的差异,而P-JNK在雌核发育二倍体鲫鲤性腺中的表达量远高于三倍体和四倍体鲫鲤的卵巢组织。此外,JNK和ERK在雌核发育二倍体鲫鲤早期性腺性原细胞中均有阳性表达。其中,JNK在10月龄雌核发育二倍体鲫鲤性腺中的阳性反应强度高于6、8月龄;而ERK在8月龄和10月龄的性腺中的阳性反应则弱于6月龄。结果表明JNK通路可能对雌核发育二倍体鲫鲤产生不减数配子具有重要调控作用。展开更多
HepatitisBvirus(HBV)infection causes acuteand chronic liver diseases,but is not directly cytopathic.Liver injury results fromrepeated attempts of the cellular immune response system to control the viral infection.Here...HepatitisBvirus(HBV)infection causes acuteand chronic liver diseases,but is not directly cytopathic.Liver injury results fromrepeated attempts of the cellular immune response system to control the viral infection.Here,we investigate the roles of cellular factors and signaling pathways involved in the regulation of HBV replication to reveal the mechanism underlying HBV infection and pathogenesis.Weshowthat collagen triple helix repeat containing 1(CTHRC1)expression is elevated in HBV-infected patients andin HBV-transfected cells through epigenetic modification and transcriptional regulation.CTHRC1 facilitates HBV replication in cultured cells and BALB/c mice by activating the PKCa/ERK/JNK/c-Jun cascade to repress the IFN/JAK/STAT pathway.HBV-activated CTHRC1 downregulates the activityof typeI interferon(IFN),theproductionof IFN-stimulatedgenes(ISGs),andthephosphorylationofsignal transducerandactivator of transcription 1/2(STAT1/2),whereas it upregulates the phosphorylation and ubiquitination of type I IFN receptors(IFNARa/b).Thus,our results showthat HBV uses a novelmechanismto hijack cellular factors and signal cascades in order to evade host antiviral immunity and maintain persistent infection.We also demonstrate that CTHRC1 has a novel role in viral infection.展开更多
文摘运用Western-blot技术和免疫组织化学来检测丝裂原活化蛋白激酶(mitogen-activated protein kinases,MAPKs)家族成员细胞外调节蛋白激酶(extracellular regulated protein kinase,ERK)和c-Jun氨基末端激酶(c-Jun N-terminal kinase,JNK)在不同生殖特性鲫鲤杂交鱼性腺组织中的表达。研究表明,JNK、ERK在鱼类性腺组织中均有较高量的表达,但在鱼类卵巢和精巢间、雌核发育二倍体鲫鲤和不同倍性鱼的性腺组织间,JNK或ERK的表达量并不存在明显的差异,而P-JNK在雌核发育二倍体鲫鲤性腺中的表达量远高于三倍体和四倍体鲫鲤的卵巢组织。此外,JNK和ERK在雌核发育二倍体鲫鲤早期性腺性原细胞中均有阳性表达。其中,JNK在10月龄雌核发育二倍体鲫鲤性腺中的阳性反应强度高于6、8月龄;而ERK在8月龄和10月龄的性腺中的阳性反应则弱于6月龄。结果表明JNK通路可能对雌核发育二倍体鲫鲤产生不减数配子具有重要调控作用。
基金supported by research grants from theMajor State Basic ResearchDevelopment Program(973 Program)(grant number 2012CB518900)the National Natural Science Foundation of China(grant numbers 31230005,31270206,31200134,and 81171525)+1 种基金the National Mega Project on Major Infectious Disease Prevention(grant numbers 2012ZX10002006-003 and 2012ZX10004-207)the Chinese Foundation for Hepatitis Prevention and Control(grant number CFHPC20132153).
文摘HepatitisBvirus(HBV)infection causes acuteand chronic liver diseases,but is not directly cytopathic.Liver injury results fromrepeated attempts of the cellular immune response system to control the viral infection.Here,we investigate the roles of cellular factors and signaling pathways involved in the regulation of HBV replication to reveal the mechanism underlying HBV infection and pathogenesis.Weshowthat collagen triple helix repeat containing 1(CTHRC1)expression is elevated in HBV-infected patients andin HBV-transfected cells through epigenetic modification and transcriptional regulation.CTHRC1 facilitates HBV replication in cultured cells and BALB/c mice by activating the PKCa/ERK/JNK/c-Jun cascade to repress the IFN/JAK/STAT pathway.HBV-activated CTHRC1 downregulates the activityof typeI interferon(IFN),theproductionof IFN-stimulatedgenes(ISGs),andthephosphorylationofsignal transducerandactivator of transcription 1/2(STAT1/2),whereas it upregulates the phosphorylation and ubiquitination of type I IFN receptors(IFNARa/b).Thus,our results showthat HBV uses a novelmechanismto hijack cellular factors and signal cascades in order to evade host antiviral immunity and maintain persistent infection.We also demonstrate that CTHRC1 has a novel role in viral infection.
