التفاصيل البيبلوغرافية
| العنوان: |
Deficiency of Trex1 leads to spontaneous development of type 1 diabetes. |
| المؤلفون: |
Zhao, Jiang-Man, Su, Zhi-Hui, Han, Qiu-Ying, Wang, Miao, Liu, Xin, Li, Jing, Huang, Shao-Yi, Chen, Jing, Li, Xiao-Wei, Chen, Xia-Ying, Guo, Zeng-Lin, Jiang, Shuai, Pan, Jie, Li, Tao, Xue, Wen, Zhou, Tao |
| المصدر: |
Nutrition & Metabolism; 1/2/2024, Vol. 21 Issue 1, p1-13, 13p |
| مصطلحات موضوعية: |
DISEASE progression, AUTOANTIBODIES, CATARACT, CYTOKINES, PANCREAS, INFLAMMATION, ANIMAL experimentation, TYPE 1 diabetes, BLOOD sugar, RNA, INTERFERONS, RATS, INSULIN, ENZYME-linked immunosorbent assay, RESEARCH funding, POLYMERASE chain reaction, DIABETIC nephropathies |
| مستخلص: |
Background: Type 1 diabetes is believed to be an autoimmune condition, characterized by destruction of insulin-producing cells, due to the detrimental inflammation in pancreas. Growing evidences have indicated the important role of type I interferon in the development of type 1 diabetes. Methods: Trex1-deficient rats were generated by using CRISPR-Cas9. The fasting blood glucose level of rat was measured by a Roche Accuchek blood glucose monitor. The levels of insulin, islet autoantibodies, and interferon-β were measured using enzyme-linked immunosorbent assay. The inflammatory genes were detected by quantitative PCR and RNA-seq. Hematein-eosin staining was used to detect the pathological changes in pancreas, eye and kidney. The pathological features of kidney were also detected by Masson trichrome and periodic acid-Schiff staining. The distribution of islet cells, immune cells or ssDNA in pancreas was analyzed by immunofluorescent staining. Results: In this study, we established a Trex1-deletion Sprague Dawley rat model, and unexpectedly, we found that the Trex1−/− rats spontaneously develop type 1 diabetes. Similar to human diabetes, the hyperglycemia in rats is accompanied by diabetic complications such as diabetic nephropathy and cataract. Mechanistical investigation revealed the accumulation of ssDNA and the excessive production of proinflammatory cytokines, including IFN-β, in Trex1 null pancreas. These are likely contributing to the inflammation in pancreas and eventually leading to the decline of pancreatic β cells. Conclusions: Our study links the DNA-induced chronic inflammation to the pathogenesis of type 1 diabetes, and also provides an animal model for type 1 diabetes studies. [ABSTRACT FROM AUTHOR] |
|
Copyright of Nutrition & Metabolism is the property of BioMed Central and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
Full Text Finder