Immunohistochemical study on hypoxia in spontaneous polycystic liver and kidney disease in rats

Hypoxia-inducible factor (HIF) mediates homeostatic responses to hypoxia and activates transcription of hypoxia-inducible genes including vascular endothelial growth factor (VEGF). The aim of this study was to examine the expressions of VEGF, HIF-1alpha and HIF-3alpha in spontaneously occurring hepatorenal polycystic lesions in two Sprague-Dawley (Crj:CD) rats. Hepatic multiple cysts were derived from the interlobular and large bile ducts, while renal cysts were from the collecting ducts and distal tubuli. These findings were confirmed by a lectin peanut agglutinin (PNA) histochemistry. In the polycystic liver, VEGF immunoreaction was strongly evident in the cytoplasm of hepatocytes, whereas expression of HIF-3alpha, but not HIF-1alpha, was found in a few nuclei of hepatocytes. In the polycystic kidney, VEGF immunoreaction was increased in the cytoplasm of collecting ducts and distal tubuli, whereas nuclear expression of HIF-1alpha and HIF-3alpha was evident in the proximal tubuli and thin loop of Henle, respectively. The results suggest that hypoxia-related molecules may be induced by cystic alterations in a heterogeneous appearance.