NFE2L2 and diabetic kidney disease: Moreover, a recent mechanistic study suggests that the GPER-mediated protective role of icariin against the high glucose-induced accumulation of EM proteins and oxidative stress in diabetic nephropathy could involve Nrf-2 signaling, because icariin augments the expression, nuclear translocation, and downstream signaling of Nrf2 in high glucose-treated human mesangial cell lines [45].