TypeIinositol 1, 4, 5-triphosphate receptors increase in kidney of mice with fulminant hepatic failure

Abstract

To delineate the mechanisms of renal vasocon-striction in hepatorenal syndrome (HRS), we investigated the expression of type I inositol 1, 4, 5-triphosphate receptors (IP3RI) of kidney in mice with fulminant hepatic failure (FHF). FHF was induced by lipopolysaccharide (LPS) in D-galactosamine (GalN) sensitized BALB/c mice. There were 20 mice in normal saline (NS)-treated group, 20 mice in LPS-treated group, 20 mice in GalN-treated group, and 60 mice in GalN/LPS-treated group (FHF group). Liver and kidney tissues were obtained at 2, 6, and 9 h after administration. The liver and kidney specimens were stained with hematoxylin-eosin for studying morphological changes under light microscope. The expression of IP3RI in kidney tissue was tested by immunohistochemistry, Western blot and reverse transcription (RT)-PCR. Kidney tissues were morphologically normal at all time points in all groups. IP3RI proteins were found localized in the plasma region of glomerular mesangial cells (GMC) and vascular smooth muscle cells (VSMC) in kidney by immunohistochemical staining. In kidney of mice with FHF at 6 h and 9 h IP3RI staining was up-regulated. Results from Western blot demonstrated consistent and significant increment of IP3RI expression in mice with FHF at 6 h and 9 h (t=3.16, P<0.05; t=5.43, P<0.01). Furthermore, we evaluated IP3RI mRNA expression by RT-PCR and observed marked up-regulation of IP3RI mRNA in FHF samples at 2 h, 6 h and 9 h compared to controls (t=2.97, P<0.05; t=4.42, P<0.01; t=3.81, P<0.01). The expression of IP3RI protein increased in GMC and renal VSMC of mice with FHF, possibly caused by up-regulation of IP3RI mRNA.