Apelin inhibited epithelial-mesenchymal transition of podocytes in diabetic mice through downregulating immunoproteasome subunits β5i

The epithelial-mesenchymal transition (EMT) of podocytes had been reported to be involved in the glomerular fibrosis in diabetic kidney diseases, which was regulated by TGF beta and NFKB pathways. And apelin, an adipokine which is upregulated in diabetic kidney diseases, was reported to be negatively correlated to TGF beta in polycystic kidney disease and attenuate EMT in renal tubular cells. Therefore, it is hypothesized that apelin might inhibit the EMT of podocytes through downregulating the expression and activation of TGF beta/Smad pathway in diabetic kidney diseases. The results showed that apelin in glomeruli of diabetic mice were increased and exogenous apelin inhibited the EMT of podocytes in diabetic mice, which were accompanied with the decreased expression of proteasome subunits beta 5i. The results from beta 5iKO mice confirmed that the inhibiting effects of apelin on EMT of podocytes in diabetic mice were dependent on beta 5i. The results from culture podocytes showed that apelin decreased the degradation of pI kappa B and promoted the translocation of I kappa B into nucleus through decreasing the expression of beta 5i, which would inhibit the promoting effects of NF kappa B on expression of TGF beta and followed by decreased activation of Smad pathway and EMT in podocytes. In conclusion, apelin might act as an EMT suppressor for podocytes to decrease the process of glomerular fibrosis in diabetic mice.