Abstract | BACKGROUND:
Type 1 diabetes is one of the chronic autoimmune diseases. Its features include the immune-triggered pancreatic beta-cells destruction. Ubiquitin ligases RNF20 and RNF40 have been discovered to participate into beta cells gene expression, insulin secretion, and expression of vitamin D receptors (VDRs). However, no reports about the role of RNF20/RNF40 in type 1 diabetes are known till now. The aim of this study was to clarify the role of RNF20/RNF40 in type 1 diabetes and explore the mechanism. METHODS: RESULTS: STZ was used to stimulate mice model for type 1 diabetes. At first, both RNF20 and RNF40 expressions were down-regulated in STZ-mediated type 1 diabetes. Additionally, RNF20/RNF40 improved hyperglycemia in STZ-stimulated mice. Moreover, RNF20/RNF40 relieved pancreatic tissue injury in STZ-induced mice. Further experiments found that RNF20/RNF40 rescued the strengthened inflammation mediated by STZ treatment. The cell apoptosis was enhanced in the pancreatic tissues of STZ-triggered mice, but this effect was weakened by overexpression of RNF20/RNF40. Besides, the VDR expression was positively regulated by RNF20/RNF40. Finally, VDR knockdown reversed improved hyperglycemia, inflammation, and cell apoptosis stimulated by overexpression of RNF20/RNF40. CONCLUSION: Our findings proved that RNF20/RNF40 activated VDR to relieve type 1 diabetes. This work might highlight the functioning of RNF20/RNF40 in the treatment of type 1 diabetes.
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Authors | Junxiang Liu, Xuri Wu, Haixia Qin, Ying Hu, Zhiyun Zhang, Yanmei Wang, Jinlan Li |
Journal | Allergologia et immunopathologia
(Allergol Immunopathol (Madr))
Vol. 51
Issue 4
Pg. 1-9
( 2023)
ISSN: 1578-1267 [Electronic] Singapore |
PMID | 37422774
(Publication Type: Journal Article)
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Chemical References |
- Streptozocin
- Ubiquitin-Protein Ligases
- Receptors, Calcitriol
- Insulin
- RNF20 protein, mouse
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Topics |
- Animals
- Mice
- Streptozocin
- Ubiquitin-Protein Ligases
(genetics, metabolism)
- Receptors, Calcitriol
(genetics)
- Diabetes Mellitus, Type 1
- Insulin
(metabolism)
- Hyperglycemia
- Disease Models, Animal
- Inflammation
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