Ren J, Wang L, Chen Z, Ma Z M, Zhu H G, Yang D L, Li X Y, Wang B I, Fei J, Wang Z G, Wen Y M
Key laboratory of Medical Molecular Virology, Institute of Medical Microbiology, Shanghai Medical College, Fudan University, Shanghai, China.
J Med Virol. 2006 May;78(5):551-60. doi: 10.1002/jmv.20575.
Hepatitis B virus (HBV)-associated nephritis has been reported worldwide. Immune complex deposition has been accepted as its pathogenesis, although the association between the presence of local HBV DNA and viral antigen and the development of nephritis remains controversial. To understand better the roles played by HBV protein expression in the kidney, the global gene expression profile was studied in the kidney tissue of a lineage of HBV transgenic mouse (#59). The mice expressed HBsAg in serum, and HBsAg and HBcAg in liver and kidney, but without virus replication. Full-length HBV genome (adr subtype, C genotype) isolated from a chronic HBV carrier was used to establish the transgenic mice #59. Similarly manipulated mice that did not express HBV viral antigens served as controls. Southern blotting, hybridization with HBV probe, and immuno-histochemical staining were used to study HBV gene expression. mRNA extracted from the kidney tissue was analyzed using Affymetrix microarrays. HBsAg and HBcAg were located mainly in the cytoplasm of tubular epithelium. Altogether 520 genes were "up-regulated" more than twofold and 76 genes "down-regulated" more than twofold in the kidney. The complement activation, blood coagulation, and acute-phase response genes were markedly "up-regulated". Compared to the controls, the level of serum C3 protein was decreased in #59 mice, while the level of C3 protein from kidney extract was increased. Results indicate that expression of HBsAg and HBcAg in tubular epithelial cells of the kidney per se can up-regulate complement-mediated inflammatory gene pathways, in addition to immune complex formation.
乙型肝炎病毒（HBV）相关性肾炎已在全球范围内被报道。免疫复合物沉积被认为是其发病机制，尽管局部HBV DNA和病毒抗原的存在与肾炎发展之间的关联仍存在争议。为了更好地理解HBV蛋白表达在肾脏中所起的作用，我们对一个HBV转基因小鼠品系（#59）的肾脏组织进行了全基因组表达谱研究。这些小鼠血清中表达HBsAg，肝脏和肾脏中表达HBsAg和HBcAg，但无病毒复制。从一名慢性HBV携带者分离出的全长HBV基因组（adr亚型，C基因型）用于建立转基因小鼠#59。同样经过操作但不表达HBV病毒抗原的小鼠作为对照。采用Southern印迹法、与HBV探针杂交以及免疫组织化学染色来研究HBV基因表达。从肾脏组织提取的mRNA使用Affymetrix微阵列进行分析。HBsAg和HBcAg主要位于肾小管上皮细胞的细胞质中。在肾脏中，共有520个基因“上调”超过两倍，76个基因“下调”超过两倍。补体激活、凝血和急性期反应基因显著“上调”。与对照组相比，#59小鼠血清C3蛋白水平降低，而肾脏提取物中C3蛋白水平升高。结果表明，肾脏肾小管上皮细胞中HBsAg和HBcAg的表达本身除了形成免疫复合物外，还能上调补体介导的炎症基因通路。
