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.
Yoshida
T
T
Laboratory of Pathology, Toxicology Division II, Institute of Environmental Toxicology, Ibaraki, Japan. yoshida@iet.or.jp
Kuwahara
M
M
Maita
K
K
Harada
T
T
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D051792:Basic Helix-Loop-Helix Proteins; D001835:Body Weight; D019963:Clinical Chemistry Tests / Q000662:veterinary; D003560:Cysts / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D016228:Endothelial Growth Factors / Q000378:metabolism; D005260:Female; D006403:Hematologic Tests / Q000662:veterinary; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007150:Immunohistochemistry / Q000662:veterinary; D008103:Liver Cirrhosis / Q000151:congenital / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D008107:Liver Diseases / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D009929:Organ Size; D007690:Polycystic Kidney Diseases / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012097:Repressor Proteins; D012376:Rodent Diseases / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D051017:Apoptosis Regulatory Proteins; D051792:Basic Helix-Loop-Helix Proteins; D016228:Endothelial Growth Factors; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008222:Lymphokines; D012097:Repressor Proteins; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C116973:HIF3A protein, human; C424683:Hif3a protein, rat