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

S. Mogami, Hidekazu Suzuki, Hitoshi Tsugawa, Seiichiro Fukuhara, T. Hibi

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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. Key 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 & Inferences: 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.

Original languageEnglish
JournalNeurogastroenterology and Motility
Volume25
Issue number7
DOIs
Publication statusPublished - 2013 Jul

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Interstitial Cells of Cajal
Pyloric Antrum
Heme Oxygenase-1
Experimental Diabetes Mellitus
Streptozocin
Stomach
Up-Regulation
Injections
Receptor Protein-Tyrosine Kinases
Type 1 Diabetes Mellitus
Fluorescent Antibody Technique
Wistar Rats
Western Blotting
Staining and Labeling
Control Groups

Keywords

  • Diabetes
  • M2 macrophage
  • Oxidative stress

ASJC Scopus subject areas

  • Endocrine and Autonomic Systems
  • Gastroenterology
  • Physiology

Cite this

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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. Key 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 & Inferences: 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.",
keywords = "Diabetes, M2 macrophage, Oxidative stress",
author = "S. Mogami and Hidekazu Suzuki and Hitoshi Tsugawa and Seiichiro Fukuhara and T. Hibi",
year = "2013",
month = "7",
doi = "10.1111/nmo.12122",
language = "English",
volume = "25",
journal = "Neurogastroenterology and Motility",
issn = "1350-1925",
publisher = "Wiley-Blackwell",
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T1 - 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

AU - Mogami, S.

AU - Suzuki, Hidekazu

AU - Tsugawa, Hitoshi

AU - Fukuhara, Seiichiro

AU - Hibi, T.

PY - 2013/7

Y1 - 2013/7

N2 - 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. Key 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 & Inferences: 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.

AB - 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. Key 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 & Inferences: 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.

KW - Diabetes

KW - M2 macrophage

KW - Oxidative stress

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