Enhancement of epithelial sodium channel expression in renal cortical collecting ducts cells by advanced glycation end products

Chiz Tzung Chang, Mai Szu Wu, Ya Chung Tian, Kuan Hsing Chen, Chun Chen Yu, Chang Hui Liao, Cheng Chieh Hung, Chih Wei Yang

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background. The epithelial sodium channel (ENaC) is a complex, and the αENaC subunit has a crucial role in sodium uptake induced by aldosterone in the distal nephron. Although experimental animal models of diabetes have demonstrated up-regulation of αENaC expression in renal cortical collecting duct (CCD) cells, the molecular mechanism remains unclear. Advanced glycation end products (AGEs) are by-products of long-term hyperglycaemia and comprise a significant pathogenic factor in diabetic nephropathy. We hypothesize that AGEs play a role in regulating αENaC gene expression. Methods. Mouse CCD cells (mpkCCDcl4) were cultured with AGE to determine the effects of AGE on αENaC expression and sodium uptake. Gene expressions of ENaC were measured by real-time PCR and sodium uptake was measured with fluorescent dye as a sodium indicator (SBFI-AM). This study analysed mitogen-activated protein kinases signalling pathways by western blotting. Cells co-transfected with plasmids of the αENaC promoter carrying a luciferase reporter and plasmids expressing wild-type or mutant serum- and glucocorticoid-induced kinase 1 (Sgk1) mRNA were stimulated with AGE to identify the signalling pathway. Results. The AGEs, stimulated in a time- and dose-dependent manner, enhanced αENaC mRNA expression and sodium uptake in mpkCCDcl4 cells. The AGEs also significantly stimulated Sgk1 mRNA and Sgk1 activity in a time- and dose-dependent manner. Co-transfected with plasmid expressing mutant Sgk1 significantly limited stimulated αENaC promoter-driven luciferase activity by AGEs in mpkCCDcl4 cells. Conclusion. Experimental results indicate that AGEs induced αENaC expression and increased sodium uptake in renal CCD cells. The mechanism through which AGEs activate αENaC expression may be via activation of Sgk1 in mpkCCDcl4 cells.

Original languageEnglish
Pages (from-to)722-731
Number of pages10
JournalNephrology Dialysis Transplantation
Volume22
Issue number3
DOIs
Publication statusPublished - Mar 2007
Externally publishedYes

Fingerprint

Epithelial Sodium Channels
Advanced Glycosylation End Products
Kidney
Glucocorticoids
Sodium
Phosphotransferases
Serum
Plasmids
Luciferases
Messenger RNA
Gene Expression
Nephrons
Diabetic Nephropathies
Mitogen-Activated Protein Kinases
Aldosterone
Fluorescent Dyes
Hyperglycemia
Real-Time Polymerase Chain Reaction
Up-Regulation
Animal Models

Keywords

  • Advanced glycation end products
  • Cortical collecting duct cells
  • Diabetic nephropathy
  • Epithelial sodium channel
  • Serum- and glucocorticoid-induced kinase

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

Enhancement of epithelial sodium channel expression in renal cortical collecting ducts cells by advanced glycation end products. / Chang, Chiz Tzung; Wu, Mai Szu; Tian, Ya Chung; Chen, Kuan Hsing; Yu, Chun Chen; Liao, Chang Hui; Hung, Cheng Chieh; Yang, Chih Wei.

In: Nephrology Dialysis Transplantation, Vol. 22, No. 3, 03.2007, p. 722-731.

Research output: Contribution to journalArticle

Chang, Chiz Tzung ; Wu, Mai Szu ; Tian, Ya Chung ; Chen, Kuan Hsing ; Yu, Chun Chen ; Liao, Chang Hui ; Hung, Cheng Chieh ; Yang, Chih Wei. / Enhancement of epithelial sodium channel expression in renal cortical collecting ducts cells by advanced glycation end products. In: Nephrology Dialysis Transplantation. 2007 ; Vol. 22, No. 3. pp. 722-731.
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abstract = "Background. The epithelial sodium channel (ENaC) is a complex, and the αENaC subunit has a crucial role in sodium uptake induced by aldosterone in the distal nephron. Although experimental animal models of diabetes have demonstrated up-regulation of αENaC expression in renal cortical collecting duct (CCD) cells, the molecular mechanism remains unclear. Advanced glycation end products (AGEs) are by-products of long-term hyperglycaemia and comprise a significant pathogenic factor in diabetic nephropathy. We hypothesize that AGEs play a role in regulating αENaC gene expression. Methods. Mouse CCD cells (mpkCCDcl4) were cultured with AGE to determine the effects of AGE on αENaC expression and sodium uptake. Gene expressions of ENaC were measured by real-time PCR and sodium uptake was measured with fluorescent dye as a sodium indicator (SBFI-AM). This study analysed mitogen-activated protein kinases signalling pathways by western blotting. Cells co-transfected with plasmids of the αENaC promoter carrying a luciferase reporter and plasmids expressing wild-type or mutant serum- and glucocorticoid-induced kinase 1 (Sgk1) mRNA were stimulated with AGE to identify the signalling pathway. Results. The AGEs, stimulated in a time- and dose-dependent manner, enhanced αENaC mRNA expression and sodium uptake in mpkCCDcl4 cells. The AGEs also significantly stimulated Sgk1 mRNA and Sgk1 activity in a time- and dose-dependent manner. Co-transfected with plasmid expressing mutant Sgk1 significantly limited stimulated αENaC promoter-driven luciferase activity by AGEs in mpkCCDcl4 cells. Conclusion. Experimental results indicate that AGEs induced αENaC expression and increased sodium uptake in renal CCD cells. The mechanism through which AGEs activate αENaC expression may be via activation of Sgk1 in mpkCCDcl4 cells.",
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AU - Tian, Ya Chung

AU - Chen, Kuan Hsing

AU - Yu, Chun Chen

AU - Liao, Chang Hui

AU - Hung, Cheng Chieh

AU - Yang, Chih Wei

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AB - Background. The epithelial sodium channel (ENaC) is a complex, and the αENaC subunit has a crucial role in sodium uptake induced by aldosterone in the distal nephron. Although experimental animal models of diabetes have demonstrated up-regulation of αENaC expression in renal cortical collecting duct (CCD) cells, the molecular mechanism remains unclear. Advanced glycation end products (AGEs) are by-products of long-term hyperglycaemia and comprise a significant pathogenic factor in diabetic nephropathy. We hypothesize that AGEs play a role in regulating αENaC gene expression. Methods. Mouse CCD cells (mpkCCDcl4) were cultured with AGE to determine the effects of AGE on αENaC expression and sodium uptake. Gene expressions of ENaC were measured by real-time PCR and sodium uptake was measured with fluorescent dye as a sodium indicator (SBFI-AM). This study analysed mitogen-activated protein kinases signalling pathways by western blotting. Cells co-transfected with plasmids of the αENaC promoter carrying a luciferase reporter and plasmids expressing wild-type or mutant serum- and glucocorticoid-induced kinase 1 (Sgk1) mRNA were stimulated with AGE to identify the signalling pathway. Results. The AGEs, stimulated in a time- and dose-dependent manner, enhanced αENaC mRNA expression and sodium uptake in mpkCCDcl4 cells. The AGEs also significantly stimulated Sgk1 mRNA and Sgk1 activity in a time- and dose-dependent manner. Co-transfected with plasmid expressing mutant Sgk1 significantly limited stimulated αENaC promoter-driven luciferase activity by AGEs in mpkCCDcl4 cells. Conclusion. Experimental results indicate that AGEs induced αENaC expression and increased sodium uptake in renal CCD cells. The mechanism through which AGEs activate αENaC expression may be via activation of Sgk1 in mpkCCDcl4 cells.

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