Gene expression profile of transgenic mouse kidney reveals pathogenesis of hepatitis B virus associated nephropathy.
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.
Ren
J
J
Key laboratory of Medical Molecular Virology, Institute of Medical Microbiology, Shanghai Medical College, Fudan University, Shanghai, China.
Wang
L
L
Chen
Z
Z
Ma
Z M
ZM
Zhu
H G
HG
Yang
D L
DL
Li
X Y
XY
Wang
B I
BI
Fei
J
J
Wang
Z G
ZG
Wen
Y M
YM
D000818:Animals; D002097:C-Reactive Protein / Q000235:genetics; D003176:Complement C3 / Q000235:genetics; D003593:Cytoplasm / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D005786:Gene Expression Regulation; D016679:Genome, Viral; D015433:Glomerulonephritis, Membranous / Q000209:etiology*; D006512:Hepatitis B Core Antigens / Q000235:genetics / Q000378:metabolism*; D006514:Hepatitis B Surface Antigens / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D006515:Hepatitis B virus / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D040081:Protein Array Analysis; D012333:RNA, Messenger / Q000235:genetics
D003176:Complement C3; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D012333:RNA, Messenger; D002097:C-Reactive Protein