배양한 사구체 상피세포에서 고농도 당과 후기 당화합물에 의한 P-cadherin의 변화 = High Glucose and Advanced Glycosylation Endproducts(AGE) Modulate the P-cadherin Expression in Glomerular Epithelial Cells(GEpC)

다국어 초록 (Multilingual 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)

참고문헌 (Reference)

1 Ha TS, "modulate the CD2AP expression in glomerular epithelial cells" 24 : 2005

2 Tryggvason K, "Unraveling the mechanisms of glomerular ultrafiltration:nephrin,a key component of the slit diaphragm" 10 : 2440-5, 1999

3 Schnabel E, "The tight junction protein ZO-1 is concentrated along slit diaphragms of the glomerular epithelium" 111 : 1255-63, 1990

4 Grunwald GB, "The structural and functional analysis of cadherin calcium-dependent cell adhesion molecules" Curr Opin Cell Biol 5 : 797-805, 1993

5 Asanuma K, "The role of podocytes in glomerular pathobiology" 7 : 255-9, 2003

6 Reiser J, "The glomerular slit diaphragm is a modified adherens junction" 11 : 1-8, 2000

7 Ruotsalainen V, "Role of nephrin in cell junction formation in human nephrogenesis" 157 : 1905-16, 2000

8 Ha TS, "Researches on the pathophysiology of proteinuria in diabetic nephropathy" 41 (41): 69-74, 1998

9 Ha TS, "Regulation of glomerular endothelial cell proteoglycans by glucose" 19 : 245-52, 2004

10 Vlassara H, "Protein glycation in the kidney:Role in diabetes and aging" 49 : 1795-804, 1996

11 Radice GL, "Precocious mammary gland development in P-cadherin-deficient mice" 139 : 1025-32, 1997

12 Rodewald R, "Porous substructure of the glomerular slit diaphragm in the rat and mouse" 60 : 423-33, 1974

13 Mundel P, "Podocyte biology and response to injury" 13 : 3005-15, 2002

14 Ha TS, "Pathophysiology of Proteinuria" 47 (47): 877-85, 2004

15 Fauci AS,, "Pathogenetic mechanisms of glomerular injury. In : Brady HR, Brenner BM, editors. Harrison's Internal Medicine" 1534-6, 1998

16 Xu ZG, "P-Cadherin is decreased in diabetic glomeruli and in glucose-stimulated podocytes in vivo and in vitro studies" 20 : 524-31, 2005

17 Chugh SS, "Molecular structure-function relationship in the slit diaphragm" 23 : 544-55, 2003

18 Tryggvason K, "Molecular basis of glomerular permselectivity" 10 : 543-9, 2001

19 Dreyer SD, "LMX1B transactivation and expression in nail-patella syndrome" 9 : 1067-74, 2000

20 Kreisberg JI, "Isolation and characterization of rat glomerular epithelial cells in vitro" 14 : 21-30, 1978

21 Goto S, "Involvement of R-cadherin in the early stage of glomerulogenesis" 9 : 1234-41, 1998

22 Westberg NG, "Human glomerular basement membrane chemical composition in diabetes mellitus" 194 : 39-47, 1973

23 Scandling J, "Glomerular size- selectivity and micro-albuminuria in early diabetic glomerular disease" 41 : 840-6, 1992

24 Vleminckx K, "Genetic manipulation of E- cadherin expression by epithelial tumour cells reveals an invasion suppressor role" 66 : 107-19, 1991

25 Nakopoulou L, "Evaluation of E-cadherin/catenin complex in primary and secondary glomerulonephritis" 39 : 469-74, 2002

26 Ha TS, "Effects of high glucose and advanced glycosylation endproducts on the α-actinin-4 expressed by glomerular epithelial cells" 23 : 694-702, 2004

27 Ha TS, "Effects of high glucose and advanced glycosylation endproducts on the in vitro permeability model using semipermeable membrane" 12 : 835-, 2001

28 Ha TS, "Effects of high glucose and advanced glycosylation endproducts on the ZO-1 expression in glomerular epithelial cells" 8 : 138-48, 2004

29 Song CJ, "Effects of angiotensin II on glomerular epithelial cells permeability model;role of oxidative stress" 23 : 396-404, 2004

30 Ha TS, "Effects of advanced glycation endproducts on rat glomerular epithelial cells:Roles of reactive oxygen species" 22 : 285-93, 2003

31 Singh AK, "Effect of glycated proteins on the matrix of glomerular epithelial cells" 9 : 802-10, 1998

32 Oh J, "Dynamic(re)organization of the podocyte actin cytoskeleton in the nephrotic syndrome" 19 : 130-7, 2004

33 Goodwin M, "Classical cadherin adhesion molecules : coordinating cell adhesion, signaling and the cytoskeleton J Mol Histol" 35 : 839-44, 2004

34 Geiger B, "Cadherins" 8 : 307-32, 1992

35 Shimoyama Y, "Cadherin cell adhesion molecules in human epithelial tissues and carcinomas" 49 : 2128-33, 1989

36 Yaoita E,, "Cadherin and catenin staining in podocytes in development and puromycin aminonucleoside nephrosis Nephrol Dial Transplant" 17 (17): 9 16-9, 2002

37 Sharma K, "Biochemical events and cytokine interactions linking glucose metabolism to the development of diabetic nephropathy" 17 : 80-92, 1997

38 Otero K, "Albumin- derived advanced glycation end-products trigger the disruption of the vascular endothelial cadherin complex in cultured human and murine endothelial cells" 359 : 567-74, 2001

39 Bains R, "A quantitative immunofluorescence study of glomerular cell adhesion proteins in proteinuric states" 183 : 272-80, 1997