中文摘要
本项目的科学问题：持续表达的乙肝表面抗原（HBsAg）与宿主细胞间作用机理及其意义。研究结果：1．发现乙肝肾病的又一机制。转基因鼠肾脏表达HBsAg导致补体激活、急性反应等通路活化，且肾脏中C3量增多，血清中减少，揭示除抗原-抗体复合物引起肾病外的又一新机制。2．HBsAg促进cyclophilin A（CypA）向胞外分泌与炎症相关。HBsAg通过与CypA结合促进CypA分泌至胞外。在转基因鼠血清及乙肝患者血清中CypA量也升高。用高压尾静脉注入法证明胞外CypA可致炎症细胞浸润。3．HBsAg表达可上调截短及全长转录调控因子LEF-1（lymphoid enhancer binding factor 1）的表达。对肝癌及癌旁组织的配对研究，发现LEF-1与HBsAg表达成正相关；在癌组织中，LEF-1 主要存在核内或胞浆内，在癌旁组织中LEF-1则主要在胞浆中，分析认为在癌前期HBsAg上调LEF-1及下游基因，促进细胞增殖，提示HBsAg可在癌前期起促癌作用。证实GRP78在HBsAg促肝细胞凋亡中起作用；HBV复制可下调细胞瘦素受体表达。
英文摘要
The aim of this project was to study the interactions between hepatitis B surface antigen (HBsAg) and host cells using HBsAg secreting cell lines and a serum HBsAg positive transgenic mouse model established in our lab, compared to their control counterparts. Transcriptomic and proteomic technology were employed together with biochemical and molecular biological technologies.Results are shown as follows: 1. An alternative pathogenesis was revealed in HBV associated nephropathy. Transcriptomic analysis was used to study the up- and down-regulations of genes in liver and kidney tissues in HBsAg transgenic mice in contrast to that of the control mice. Predominantly, enzymes involved in polysaccharide and lipid metabolism were deregulated in liver tissues of transgenic mice. Expression of HBsAg and HBcAg in tubular epithelial cells of the kidney up-regulated complement-mediated inflammatory gene pathways, unrelated to immune complex formation. Compared to the controls, the level of serum C3 protein was decreased in transgenic mice, while the level of C3 protein from kidney extract was increased. This revealed an alternative pathogenesis for HBV associated nephropathy.2. HBsAg induced extracellular secretion of cyclophilin A ( CypA) which was associated with inflammatory responses. Expression of HBsAg induced secr
结题摘要
本项目的科学问题：持续表达的乙肝表面抗原（HBsAg）与宿主细胞间作用机理及其意义。研究结果：1．发现乙肝肾病的又一机制。转基因鼠肾脏表达HBsAg导致补体激活、急性反应等通路活化，且肾脏中C3量增多，血清中减少，揭示除抗原-抗体复合物引起肾病外的又一新机制。2．HBsAg促进cyclophilin A（CypA）向胞外分泌与炎症相关。HBsAg通过与CypA结合促进CypA分泌至胞外。在转基因鼠血清及乙肝患者血清中CypA量也升高。用高压尾静脉注入法证明胞外CypA可致炎症细胞浸润。3．HBsAg表达可上调截短及全长转录调控因子LEF-1（lymphoid enhancer binding factor 1）的表达。对肝癌及癌旁组织的配对研究，发现LEF-1与HBsAg表达成正相关；在癌组织中，LEF-1 主要存在核内或胞浆内，在癌旁组织中LEF-1则主要在胞浆中，分析认为在癌前期HBsAg上调LEF-1及下游基因，促进细胞增殖，提示HBsAg可在癌前期起促癌作用。证实GRP78在HBsAg促肝细胞凋亡中起作用；HBV复制可下调细胞瘦素受体表达。