Protective effect of hedgehog signaling on cytokine-induced cytotoxicity in pancreatic beta-cells

H. Umeda, N. Ozaki, N. Mizutani, T. Fukuyama, H. Nagasaki, H. Arima, Y. Oiso

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: Hedgehog (Hh) signaling plays an important role in pancreas development. However, its role in the developed endocrine pancreas remains to be elucidated. To clarify whether Hh signaling participates in beta-cell survival, we investigated the role of Hh signaling in cytokine-induced apoptosis in pancreatic beta-cells. Methods: Insulin-producing INS-1E cells were transfected with Sonic Hh (Shh) expression vector or siRNA against Indian Hh (siIhh). The Hh signal inhibitor cyclopamine were pretreated in INS-1E cells and rat islets. The cells were exposed to 200U/ml IL-1β and 200U/ml IFN-γ for 48h. Apoptosis was estimated by flow cytometory and immunofluorescence staining for cleaved caspase-3. Nitric oxide generation was measured by Griess reaction. Results: We found that exposure to proinflammatory cytokines increased Ihh expression in rat islets and INS-1E cells. Overexpression of Shh reduced cytokine-induced apoptosis. By contrast, treatment with cyclopamine increased cytokine-induced apoptosis in INS-1E cells and rat islets. Treatment with the siIhh showed same results in INS-1E cells. Forced expression of Shh suppressed cytokine-induced nuclear factor-B promoter activity, leading to attenuation of nitric oxide synthase 2 expression and nitric oxide production, while Ihh knockdown enhanced this pathway in INS-1E cells. Conclusion: Our findings suggest that Hh signaling is implicated in protecting beta-cells from cytokine-induced cytotoxicity.

Original languageEnglish
Pages (from-to)692-698
Number of pages7
JournalExperimental and Clinical Endocrinology and Diabetes
Volume118
Issue number10
DOIs
Publication statusPublished - 22-11-2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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