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

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

• Ha TS
• Koo HH
• Lee HS
• Yoon OJ

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.

Keyword

Diabetic nephropathy; Advanced glycosylation endproducts; P-cadherin; Glomerular epithelial cells; Podocyte

MeSH Terms

Animals
Blotting, Western
Cadherins*
Diabetic Nephropathies
Filtration
Glucose*
Glycosylation*
Podocytes
Polymerase Chain Reaction
Rats
RNA, Messenger
Cadherins
Glucose
RNA, Messenger