Expression of Notch-Hif-1α signaling pathway in liver regeneration of rats.

OBJECTIVE

To investigate whether the Notch-Hif-1α signaling pathway is involved in liver regeneration.

METHODS

Rats were divided into two groups and treated with daily intraperitoneal injections of saline (control) or the gamma-secretase inhibitor, Fli-06, for 2 days. Two-thirds of the rat livers were resected and rats were later euthanized at specific time points post-resection to analyze the remnant livers. Each group's liver/body weight ratio was calculated, and immunostaining and western blotting were used to determine the cell proliferation marker, PCNA and Ki-67 expression. Real-time PCR and western blotting were used to compare the mRNA expression of Notch homolog-1 (), hairy and enhancer of split-1 (), and vascular endothelial growth factor (), and the protein expression of NICD and HIF-1α, respectively.

RESULTS

The liver/body weight ratios and number of Ki-67- and PCNA-positive cells were significantly lower in the experimental group than the control group, indicating lower levels of liver regeneration following the disruption of Notch signaling by Fli-06. The and mRNA levels and NICD and HIF-1α protein expression levels were all down-regulated by Fli-06 treatment.

CONCLUSION

Notch-Hif-α signaling pathway activation plays an important role in liver regeneration, where it may contribute toward liver cell proliferation.