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

Hypoxia-inducible factor (HIF) mediates homeostatic responses to hypoxia an d activates transcription of hypoxia-inducible genes including vascular end othelial growth factor (VEGF). The aim of this study was to examine the exp ressions of VEGF HIF-1 alpha and HIF-3 alpha in spontaneously occurring hep atorenal polycystic lesions in two Sprague-Dawley (Crj:CD) rats. Hepatic mu ltiple cysts were derived from the interlobular and large bile ducts, while renal cysts were from the collecting ducts and distal tubuli. These findin gs were confirmed by a lectin peanut agglutinin (PNA) histochemistry. In th e polycystic liver, VEGF immunoreaction was strongly evident in the cytopla sm of hepatocytes, whereas expression of HIF-3 alpha, but not HIF-1 alpha, was found in a few nuclei of hepatocytes. In the polycystic kidney, VEGF im munoreaction was increased in the cytoplasm of collecting ducts and distal tubuli, whereas nuclear expression of HIF-1 alpha and HIF-3 alpha was evide nt in the proximal tubuli and thin loop of Henle, respectively. The results suggest that hypoxia-related molecules may be induced by cystic alteration s in a heterogeneous appearance.