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We have reported that tumor necrosis factor-α (TNF-α) is critical for reduction of glomerular filtration rate (GFR) in rats with fulminant hepatic failure (FHF). The present study aims to evaluate the underlying mechanisms of decreased GFR during acute hepatic failure. Rats with FHF induced by d-galactosamine plus lipopolysaccharide (GalN/LPS) were injected intravenously with recombinant lentivirus harboring short hairpin RNA against the protein kinase C-α (PKC-α) gene (Lenti-shRNA-PKC-α). GFR, serum levels of aminotransferases, creatinine, urea nitrogen, potassium, sodium, chloride, TNF-α, and endothelin-1 (ET-1), as well as type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) expression in renal tissue were assessed. The effects of PKC-αsilencing on TNF-α-induced IP3R1, specificity protein 1 (SP-1), and c-Jun NH2-terminal kinase (JNK) expression, as well as cytosolic calcium content were determined in glomerular mesangial cell (GMCs) with RNAi against PKC-α. Renal IP3R1 overexpression was abrogated by pre-treatment with Lenti-shRNA-PKC-α. The PKC-αsilence significantly improved the compromised GFR, reduced Cr levels, and reversed the decrease in glomerular inulin space and the increase in glomerular calcium content in GalN/LPS-exposed rats. TNF-α treatment increased expression of PKC-α, IP3R1, specificity protein 1 (SP-1), JNK, and p-JNK in GMCs and increased Ca2 +release and binding activity of SP-1 to the IP3R1promoter. These effects were blocked by transfection of siRNA against the PKC-αgene, and the PKC-αgene silence also restored cytosolic Ca2+concentration. RNAi targeting PKC-αinhibited TNF-α-induced IP3R1 overexpression and in turn improved compromised GFR in the development of acute kidney injury during FHF in rats.

Heat shock proteins (HSPs), which have a variety of functions, are one of the stress protein families widely exist in animal and plant environment. In recent years, more and more researches have reported that HSPs play a dual role in the process of hepatitis B virus (HBV) infection. Persistent infection caused by HBV is one of the key causes of chronic hepatitis B (CHB), cirrhosis and liver cancer. In this article, we summarized the regulatory mechanisms between the HSPs and virus especially HBV proliferation and their associated diseases based on the biological functions of stress proteins in response to viral infection and their research progress. In view of the potential of HSPs as a broad-spectrum antiviral target, we also discussed the current progress and challenges in the field of drug development based on HSPs, as well as the possible application value of chemical compounds that have been evaluated clinically in HBV treatment.