1Department of Pediatrics, Chungbuk National University 2Department of Pediatrics, Chungbuk National University 3Medical Research Institute, Chungbuk National University 4Medical Research Institute, Chungbuk National University
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ABSTRACT
Purpose : Podocytes are critical in maintaining the filtration barrier of the glomerulus and are dependent on the integrity of slit diaphragm(SD) proteins including nephrin, p-cadherin, and others. Diabetic proteinuric condition demonstrates defects in SD molecules as well as ultrastructural changes in podocytes. We examined the molecular basis for this alteration of SD molecules especially on P-cadherin as a candidate regulating the modulation of pathogenic changes in the barrier to protein filtration. Methods : To investigate whether high glucose and AGE induce changes in SD, we cultured rat GEpC under normal(5 mM) or high glucose(30 mM) and AGE- or BSA-added conditions and measured the change of P-cadherin expression by Western blotting and RT-PCR. Results : We found that administration of high glucose decreased the P-cadherin production significantly in the presence or absence of AGE by Western blotting. In RT-PCR high glucose with or without AGE also significantly decreased the expression of P-cadherin mRNA compared to those of controls. Such changes were not seen in the osmotic control. Conclusion : We suggest that high glucose with or without AGE suppresses the Production of P-cadherin at the transcriptional level and that these changes nay explain the functional changes of SD in diabetic conditions. (J Korean Soc Pediatr Nephrol 2005;9:119-127)
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