High Glucose and Advanced Glycosylation Endproducts(AGE) Modulate the P-cadherin Expression in Glomerular Epithelial Cells(GEpC)

Ha, Tae-Sun; Koo, Hyun-Hoe; Lee, Hae-Soo; Yoon, Ok-Ja

J Korean Soc Pediatr Nephrol > Volume 9(2); 2005 > Article

J Korean Soc Pediatr Nephrol 2005;9(2): 119-127.

배양한 사구체 상피세포에서 고농도 당과 후기 당화합물에 의한 P-cadherin의 변화

하태선, 구현회, 이해수, 윤옥자

¹충북대학교 의과대학 소아과학교실
²충북대학교 의과대학 소아과학교실
³충북대학교 의과대학 의학연구소
⁴충북대학교 의과대학 의학연구소

High Glucose and Advanced Glycosylation Endproducts(AGE) Modulate the P-cadherin Expression in Glomerular Epithelial Cells(GEpC)

Tae-Sun Ha, Hyun-Hoe Koo, Hae-Soo Lee, Ok-Ja Yoon

¹Department of Pediatrics, Chungbuk National University
²Department of Pediatrics, Chungbuk National University
³Medical Research Institute, Chungbuk National University
⁴Medical Research Institute, Chungbuk National University

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 may explain the functional changes of SD in diabetic conditions.

Key words: Diabetic nephropathy | Advanced glycosylation endproducts | P-cadherin | Glomerular epithelial cells | Podocyte