Il ruolo degli estrogeni nella prevenzione della disfunzione e del danno dei podociti glomerulari nella nefropatia diabetica

We recently showed that 17β-estradiol (E2) treatment ameloriated type 2 diabetic glomerulosclerosis in mice in part by protecting podocyte structure and function. Progressive podocyte damage is characterized by foot process effacement, vacuolization, detachment of podocytes from the glomerular basement membrane and apoptosis. In addition, podocytes are highly dependent on the preservation of their actin cytoskeleton to ensure proper function and survival. Since E2 administration prevented podocyte damage in our study on diabetic db/db mice, and has been shown to regulate both actin cytoskeleton and apoptosis in other cells types and tissues, we investigated whether actin remodeling and apoptosis were prevented in podocytes isolated from E2 treated diabetic db/db mice as compared to placebo. We performed G-actin/F-actin assays, western analysis for Hsp25 expression, Rac1 activity and apoptosis assays on previously characterized podocytes isolated from both in vivo treated placebo and E2 female db/db mice. We found that in vivo E2 protects against a phenotype change in the cultured podocytes with an increase in F-actin versus G-actin, decrease in Hsp25 expression and transcriptional activation, increase of Rac1 activity and decrease apoptotic intermediates. Based on these results we 17 conclude that E2 treatment protects against podocyte damage and may prevent/reduce diabetes-induced kidney disease.