Abstract: FR-PO605

Pioglitazone Stabilizes Nephrin Expression via SUMOylation

Session Information

Category: Diabetes

  • 501 Diabetes Mellitus and Obesity: Basic - Experimental

Authors

  • Schaefer, Irini, Hannover Medical School, Nephrology , Hannover, Germany
  • Schiffer, Mario, Hannover Medical School, Nephrology , Hannover, Germany
  • Haller, Hermann G., Hannover Medical School, Nephrology , Hannover, Germany
Background

Pioglitazone belongs to a group of thiazoldinediones, antihypergycaemic drugs that increase peripheral insuline sensitivity. As peroxisome proliferator-activated receptor (PPAR) agonists they have been demonstrated to significantly decrease urinary albumin excretion in patients with type-2 diabetes. Furthermore, treatment with pioglitazone exerts anti-apoptotic effects on podocytes. However, the nephroprotective effects on a cellular and molecular level of these drugs remain elusive. We have investigated the effects of pioglitazone-treatment on nephrin expression “in vitro”.

Methods

Differentiated podocytes were treated with 20 µm pioglitazone over 72 hours and western blot was performed. Subcellular fractionation shows expression of nephrin in the compartments. To show if pioglitazone also stabilize nephrin in "aged" podocytes we differentiated them over 8 weeks. Immunoprecipitation were performed for analyzing SUMOylation of neprin after treatment with pioglitazone.

Results

We found that nephrin expression was strongly enhanced in human and murine podocytes after pioglitazone exposure. Subcellular fractionation shows that the enhanced neprin expression was restricted to the plasma membrane. When we "aged" podocytes in vitro by keeping them under differentiating conditions for more than 8 weeks we detected a significant decrease of nephrin expression under normal culture conditions. However, nephrin expression remained stable over 8 weeks in the presence of pioglitazone. Interestingly, we found that SUMOylation of nephrin was significantly enhanced in the presence of pioglitazone.

Conclusion

Our data strongly suggest that membrane expression of nephrin in podocytes is modulated by pioglitazone treatment. The strong expression of nephrin in cultivated podocytes after treatment with pioglitazone indicates a direct molecular mechanism which is most likely responsible for the renoprotective and anti-proteinuric effects of pioglitazone treatments in vivo.

Funding

  • Government Support - Non-U.S.