β-Cell DNA Damage Response Promotes Islet Inflammation in Type 1 Diabetes
| العنوان: | β-Cell DNA Damage Response Promotes Islet Inflammation in Type 1 Diabetes |
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| المؤلفون: | Noa Weinberg-Corem, Yuval Dor, Sigurd Lenzen, Avital Swisa, Benjamin Glaser, Elad Horwitz, Knut Dahl-Jørgensen, Maya Fischman, Agnes Klochendler, Marcela Brissova, Anne Jörns, Sophia Zhitomirsky, Tsuria Lax, Lars Krogvold, Alvin C. Powers, Tehila Dahan, Noa Hurvitz |
| المصدر: | Diabetes |
| بيانات النشر: | American Diabetes Association, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Adult, Male, 0301 basic medicine, endocrine system, endocrine system diseases, DNA repair, DNA damage, Endocrinology, Diabetes and Metabolism, Inflammation, medicine.disease_cause, Diabetes Mellitus, Experimental, Autoimmunity, Islets of Langerhans, Mice, Young Adult, 03 medical and health sciences, Insulin-Secreting Cells, Internal Medicine, medicine, Animals, Humans, Autoimmune disease, geography, geography.geographical_feature_category, business.industry, nutritional and metabolic diseases, Middle Aged, Islet, medicine.disease, Streptozotocin, Diabetes Mellitus, Type 1, 030104 developmental biology, Islet Studies, Cancer research, Female, medicine.symptom, business, Ex vivo, DNA Damage, medicine.drug |
| الوصف: | Type 1 diabetes (T1D) is an autoimmune disease where pancreatic β-cells are destroyed by islet-infiltrating T cells. Although a role for β-cell defects has been suspected, β-cell abnormalities are difficult to demonstrate. We show a β-cell DNA damage response (DDR), presented by activation of the 53BP1 protein and accumulation of p53, in biopsy and autopsy material from patients with recently diagnosed T1D as well as a rat model of human T1D. The β-cell DDR is more frequent in islets infiltrated by CD45+ immune cells, suggesting a link to islet inflammation. The β-cell toxin streptozotocin (STZ) elicits DDR in islets, both in vivo and ex vivo, and causes elevation of the proinflammatory molecules IL-1β and Cxcl10. β-Cell–specific inactivation of the master DNA repair gene ataxia telangiectasia mutated (ATM) in STZ-treated mice decreases the expression of proinflammatory cytokines in islets and attenuates the development of hyperglycemia. Together, these data suggest that β-cell DDR is an early event in T1D, possibly contributing to autoimmunity. |
| تدمد: | 1939-327X 0012-1797 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a3e3de0a054b8dcdf74d30d164591abaTest https://doi.org/10.2337/db17-1006Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a3e3de0a054b8dcdf74d30d164591aba |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1939327X 00121797 |
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