Endocrine Abstracts

Activation of mineralocorticoid receptor (MR) is shown in diabetic pathophysiology. We have investigated the activation mechanism of MR protein in diabetic nephropathy and clarified one of the mechanisms of activation of MR protein by hyperglycemia. On the other hand, MR is abundantly expressed in the retina. Retinal Müller glial cells are known to be involved in the control of retina hydration and homeostasis of potassium through MR and it is reported that treatment of MR antagonist is effective in central serous chorioretinopathy that causes edema between retina and choroid. Therefore, it is suggested that MR may be involved in edematous diseases of the retina. In diabetic macular edema, the role of VEGF has been demonstrated in recent studies, but a detailed mechanism of edema remains largely unknown. In this study, we confirmed the MR pathway in human retinal Müller glial cells and observed the response by hyperglycemia stimulation. We examined the MR pathway with MIO-M1 cell line which is a naturally immortalized retinal Müller glial cell line derived from human retina. We confirmed that MR proteins and mRNA are expressed in MIO-M1 cells by Western blotting and real time RT-PCR. Furthermore, we confirmed SGK1 and αENaC which were a target gene of the MR. We treated MIO-M1 cells with aldosterone. Aldosterone induces a significant up-regulation of MR, αENaC and SGK1 mRNA expression in MIO-M1 cells. For the examination of the diabetic retina, we treated MIO-M1 cells with high glucose (HG) condition and examined the effect of HG on MR activities. As a control, normal glucose (NG) was treated. HG treatment increased the 2.2 times MR protein levels in MIO-M1 cells (P<0.01). On the other hand, MR mRNA did not change. Regarding MR target genes, SGK1 mRNA was significantly increased in HG compared to NG (6 h: P<0.001, 12 h P<0.01) but αENaC did not change. In Müller cells of the retina, hyperglycemia stimulates MR signal activity and may be associated with aggravation of edema. In this study, MR protein was increased, but MR mRNA was not increased in hyperglycemic condition. Regarding the mechanism of increase in MR protein, it was suggested that stimulation of hyperglycemia may induce activation of the translational factor and suppression of MR protein degradation.