Transgenic Overexpression of Galectin-3 in Pancreatic β Cells Attenuates Hyperglycemia in Mice: Synergistic Antidiabetic Effect With Exogenous IL-33.
2021
Преузимање 🢃
Аутори:
Jovičić, NemanjaPetrović, Ivica
Pejnović, Nada
Ljujić, Biljana
Miletić Kovačević, Marina
Pavlović, Slađana
Jeftić, Ilija
Đukić, Aleksandar
Srejović, Ivan
Jakovljević, Vladimir
Lukić, Miodrag L.
Тип документа:
Чланак у часопису (Објављена верзија)
,
© 2021 Jovicic, Petrovic, Pejnovic, Ljujic, Miletic Kovacevic, Pavlovic, Jeftic, Djukic, Srejovic, Jakovljevic and Lukic.
Метаподаци
Приказ свих података о документуАпстракт:
Galectin-3 (Gal-3) has diverse roles in inflammatory and autoimmune diseases. There is evidence that Gal-3 plays a role in both type 1 and type 2 diabetes. While the role of Gal-3 expression in immune cells invading the pancreatic islets in the experimental model of type 1 diabetes mellitus has been already studied, the importance of the overexpression of Gal-3 in the target β cells is not defined. Therefore, we used multiple low doses of streptozotocin (MLD-STZ)-induced diabetes in C57Bl/6 mice to analyze the effect of transgenic (TG) overexpression of Gal-3 in β cells. Our results demonstrated that the overexpression of Gal-3 protected β cells from apoptosis and attenuated MLD-STZ-induced hyperglycemia, glycosuria, and ketonuria. The cellular analysis of pancreata and draining lymph nodes showed that Gal-3 overexpression significantly decreased the number of pro-inflammatory cells without affecting the presence of T-regulatory cells. As the application of exogenous interleukin 33 (IL-33) given from the beginning of MLD-STZ diabetes induction attenuates the development of disease, by increasing the presence of regulatory FoxP3+ ST2+ cells, we evaluated the potential synergistic effect of the exogenous IL-33 and TG overexpression of Gal-3 in β cells at the later stage of diabetogenesis. The addition of IL-33 potentiated the survival of β cells and attenuated diabetes even when administered later, after the onset of hyperglycemia (12-18 days), suggesting that protection from apoptosis and immunoregulation by IL-33 may attenuate type 1 diabetes.
Кључне речи:
Galectin-3; Interleukin 33 (IL-33); Regulatory T cells (T reg); Dype 1 diabetes mellitus (T1D); β cellsИзвор:
Frontiers in Pharmacology, 2021, 12, 714683-Финансирање / пројекти:
- Утицај IL-33/ST2 сигналног пута и галектина-3 у патогенези експерименталних периапикалних промена (RS-MESTD-Basic Research (BR or ON)-175071)
- Swiss National Science Foundation
- Faculty of Medical Sciences, University of Kragujevac, Serbia (JP13-17)
DOI: 10.3389/fphar.2021.714683
ISSN: 1663-9812
PubMed: 34803672
WoS: 000722354200001
Scopus: 2-s2.0-85119409943
URI
https://www.frontiersin.org/articles/10.3389/fphar.2021.714683/fullhttp://radar.ibiss.bg.ac.rs/handle/123456789/4697