title: Impaired heme oxygenase-1 induction in the gastric antrum induces disruption of the interstitial cells of Cajal network in a rat model of streptozotocin-induced diabetes.
abstract: BACKGROUND
  Streptozotocin (STZ) is known to induce type I diabetes and the loss of the interstitial cells of Cajal (ICC). However, the regulation of heme oxygenase-1 (HO-1) expression, which is reported to protect ICC, has not yet been elucidated in this model. The aim of this study was to investigate the alterations of HO-1 expression and clarify the mechanism of ICC loss in the stomach using the rat model of STZ-induced diabetes.
  
  
  METHODS
  Streptozotocin (65 mg kg(-1) ) was intraperitoneally administered to 8-week-old female Wistar rats. Cobalt protoporphyrin (CoPP), an HO-1 inducer, was administered subcutaneously once a week after the STZ injection. The expressions of HO-1 and the receptor tyrosine kinase c-Kit (a marker for ICC) proteins were investigated by western blot analysis and immunofluorescence staining.
  
  
  RESULTS
  Expression of c-Kit, particularly in the gastric antrum, was significantly decreased at 8 weeks, not at 1 week, compared to those of the control group. Significantly increased induction of HO-1 expression, especially in the gastric corpus but not in the antrum, was observed in the STZ group at 8 weeks after the STZ injection relative to control. CoPP administration significantly up-regulated HO-1 expression in the STZ diabetic group and significantly restored the previously reduced ICC in the gastric antrum.
  
  
  CONCLUSIONS
  Up-regulation of HO-1 expression in the STZ diabetic model was limited to the gastric corpus and impaired up-regulation of HO-1 expression in the gastric antrum likely induced the disruption of the ICC network.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Mogami
authors.forename: H
authors.initials: H
authors.lastname: Suzuki
authors.forename: H
authors.initials: H
authors.lastname: Tsugawa
authors.forename: S
authors.initials: S
authors.lastname: Fukuhara
authors.forename: T
authors.initials: T
authors.lastname: Hibi
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D005260:Female; D005455:Fluorescent Antibody Technique; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D056885:Interstitial Cells of Cajal / Q000201:enzymology*; D011706:Pyloric Antrum / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013311:Streptozocin; D015854:Up-Regulation
chemical_list: D013311:Streptozocin; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat