Early growth response 2 activates MAF bZIP transcription factor F to protect β-cells from oxidative stress in type 1 diabetes.

BACKGROUND

Dysfunction of insulin-secreting pancreatic β-cells is a crucial factor in the development and advancement of type 1 diabetes (T1D). This investigation delves into the role of early growth response 2 (Egr2) in the function of pancreatic β-cells and explores its functional mechanism.

METHODS

Expression of Egr2 in the pancreatic tissues of streptozotocin (STZ)-treated mice and mouse MIN6 pancreatic β-cells was examined using immunohistochemistry and RT-qPCR. Gain-of-function assays of Egr2 were performed to analyze its role in insulitis severity in mice. In vitro, the viability, apoptosis, and oxidative stress in MIN6 cells were analyzed. The downstream target of Egr2 was obtained using bioinformatics tools. The interaction between Egr2 and the promoter of MAF bZIP transcription factor F (Maff) was investigated. Silencing of Maff was introduced in these models to verify its involvement in the effects of Egr2.

RESULTS

Egr2 was poorly expressed in the pancreatic tissues of STZ-treated mice and the challenged MIN6 cells. Overexpression of Egr2 lowered insulitis score and alleviated cell apoptosis within the pancreas. This procedure also enhanced the viability of MIN6 cells while reducing STZ-induced oxidative stress and apoptosis. Maff, a downstream target of Egr2, was found to be poorly expressed in these models and restored following Egr2 overexpression. The ameliorating effects of Egr2 on STZ-induced T1D-associated symptoms were negated by the additional Maff silencing.

CONCLUSION

This study suggests that Egr2 activates transcription of Maff to protect pancreatic β-cells from oxidative stress damage and apoptosis.