Data_Sheet_1_MiR-17-5p Inhibits TXNIP/NLRP3 Inflammasome Pathway and Suppresses Pancreatic β-Cell Pyroptosis in Diabetic Mice.ZIP
Objective: Diabetes mellitus is a chronic progressive inflammatory metabolic disease with pancreatic β-cells dysfunction. The present study aimed to investigate whether miR-17-5p plays a protective effect on pancreatic β-cells function in diabetes mellitus (DM) mice and dissect the underlying mechanism.
Methods: C57BL/6J mice were randomly divided into control, DM, DM + Lentivirus negative control (LV-NC), and DM + Lenti-OE™ miR-17-5p (LV-miR-17-5) groups. DM was established by feeding a high-fat diet and intraperitoneal injection with streptozotocin (STZ) in mice. Blood glucose and glucose tolerance in circulation were measured. Meanwhile, the activation of nod-like receptor protein 3 (NLRP3) inflammasome, pancreas pyroptosis, and the expression of miR-17-5p and thioredoxin-interacting protein (TXNIP) were detected in the pancreas of DM mice. Pancreatic β-cell line INS-1 subjected to different concentrations of glucose was used in in vitro experiments.
Results: Compared with control mice, glucose tolerance deficit, elevated blood glucose level, and decreased pancreatic islet size, were presented in DM mice, which was associated with a downregulation of miR-17-5p. Importantly, exogenous miR-17-5p alleviated pancreas injury, and consequently improved glucose tolerance and decreased blood glucose in DM mice. In vitro experiments showed that high glucose decreased miR-17-5p expression and impaired insulin secretion in INS-1 cells. Mechanistically, miR-17-5p inhibited the expression of TXNIP and NLRP3 inflammasome activation, and thus decreased pancreatic β-cell pyroptosis.
Conclusion: Our results demonstrated that miR-17-5p improves glucose tolerance, and pancreatic β-cell function and inhibits TXNIP/NLRP3 inflammasome pathway-related pyroptosis in DM mice.
History
References
- https://doi.org//10.1016/j.jacc.2018.04.027
- https://doi.org//10.3390/ijms21051835
- https://doi.org//10.3390/cells10020314
- https://doi.org//10.1016/j.redox.2020.101523
- https://doi.org//10.1038/s41423-021-00740-6
- https://doi.org//10.2147/jir.S291453
- https://doi.org//10.1007/s12272-021-01307-9
- https://doi.org//10.3390/ijms22041693
- https://doi.org//10.3389/fimmu.2013.00514
- https://doi.org//10.1007/s00125-017-4542-6
- https://doi.org//10.2337/db09-1100
- https://doi.org//10.1016/j.redox.2015.01.008
- https://doi.org//10.26355/eurrev_202010_23418
- https://doi.org//10.1002/cbin.10691
- https://doi.org//10.1093/toxsci/kfv313
- https://doi.org//10.1038/s41598-020-78629-z
- https://doi.org//10.3389/fendo.2020.00009
- https://doi.org//10.1016/j.lfs.2021.119133
- https://doi.org//10.1128/iai.00732-19
- https://doi.org//10.1126/science.1184003
- https://doi.org//10.1038/s41416-020-0940-5
- https://doi.org//10.26914/c.cnkihy.2019.006110
- https://doi.org//10.1371/journal.pone.0004699
- https://doi.org//10.1016/j.molmet.2017.06.020
- https://doi.org//10.1210/me.2014-1306
- https://doi.org//10.1074/jbc.M115.698365
- https://doi.org//10.1155/2014/712781
- https://doi.org//10.1016/j.arr.2017.10.003
- https://doi.org//10.1038/cddis.2017.190
- https://doi.org//10.1016/j.biopha.2018.08.067
- https://doi.org//10.1016/j.biopha.2019.109410
- https://doi.org//10.1016/j.cmet.2012.07.007
- https://doi.org//10.1186/s12974-018-1077-9
- https://doi.org//10.1111/jcmm.15698
- https://doi.org//10.1016/j.lfs.2019.117138
- https://doi.org//10.7150/ijbs.33568
- https://doi.org//10.1080/21623945.2020.1778826
- https://doi.org//10.3390/nu12051516