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AIM: To clarify the mechanisms of renal vasoconstriction in hepatorenal syndrome (HRS) by investigating the effect of tumor necrosis actor-α (TNF-α) on the expression of type 1 inositol 1,4,5-triphosphate receptors (IP3R) in renal tissues. METHODS: Ex vivo perfused rat kidney model was used in this study. Male Wistar rats were randomly divided into 3 groups: control group (group A), heparin (10 mg/L) treatment group (group B), and TNF-α (1 μg/L) treatment group (group C). After perfusion, immunohistochemical staining, Western blot, and real-time quantitative polymerase chain reaction (RTQ-PCR) were used to detect the distribution and expression of type 1 IP3R in renal tissues. RESULTS: Immunohistochemical staining showed that type 1 IP3R protein was localized at the plasma region of glomerular mesangial cells and vascular smooth muscle cells in rat kidney, and the number of positive cells was significantly higher in group C than that in group A (U = 2.26, P < 0.05). However, there was no marked difference between group A and B (P > 0.05). Western blot demonstrated a consistent result with immunohistochemistry did. The protein expression of type 1 IP3R was significant higher in group C than that in group A (1.89 ± 0.11 vs 0.55 ± 0.03, P < 0.05), and there was no marked difference between group A and B (P > 0.05). RTQPCR showed that the mRNA expression of type 1 IP3R was dramatically increased in group C as compared with that in group A (7.99 ± 0.12 vs 1.00 ± 0.05, P < 0.05), and no marked difference exists between group A and B (P > 0.05). CONCLUSION: TNF-α can enhance the protein and mRNA expression of type1 IP3R in glomerular mesangial cells and vascular smooth muscle cells from kidney.

Tumor necrosis factor-α enhances the expression of type 1 inositol 1,4,5-triphosphate receptors