Reduced levels of insulin-like growth factor-1 receptor (IGF-1R) suppress cellular signaling in experimental autoimmune sialadenitis (EAS).
The nonobese diabetic mouse (NOD) develops destruction and functional impairment of salivary and lachrymal glands, experimental autoimmune sialadenitis (EAS), resembling and representing a model for Sjogren's syndrome (SS). To investigate the mechanisms of tissue destruction in EAS, we analyzed a cell survival promoter insulin-like growth factor-1 receptor (IGF-1R) in the submandibular glands of NOD mice with this disease. We also evaluated the expression of a downstream effector of IGF-1R, BAD. Receptor-binding autoradiography revealed that the IGF-1R levels in submandibular glands from young NOD mice were lower than those in adult NOD mice. Immunofluorescence staining demonstrated that BAD expression in the epithelial cells of the submandibular gland was consistently enhanced throughout the course of EAS in NOD mice. These findings suggest that a reduction in the levels of IGF-1R induces a defective glandular homeostasis in the submandibular gland epithelial cells and triggers EAS.
Mustafa
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Division of Periodontics, Karolinska Institute, Institute of Odontology, Stockholm, Sweden.
Mustafa
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Elbakri
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Link
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Adem
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D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology / Q000378:metabolism*; D001345:Autoradiography; D002352:Carrier Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006706:Homeostasis; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D012793:Sialadenitis / Q000209:etiology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D012859:Sjogren's Syndrome / Q000378:metabolism; D013363:Submandibular Gland / Q000378:metabolism; D051025:bcl-Associated Death Protein
C494819:BAD protein, human; C494820:Bad protein, mouse; D002352:Carrier Proteins; D051025:bcl-Associated Death Protein; D017526:Receptor, IGF Type 1