The role of SGK-1 in angiotensin II-mediated sodium reabsorption in human proximal tubular cells

Veronica A. Stevens, Sonia Saad, Philip Poronnik, Carol A. Fenton-Lee, Tania S. Polhill, Carol A. Pollock*

*Corresponding author for this work

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Background. The role of angiotensin II (Ang II) in mediating excessive sodium reabsorption in diabetic nephropathy is recognized. Serine-glucocorticoid kinase-1 (SGK-1) increases sodium-hydrogen exchanger-3 (NHE3) expression and is known to be upregulated in in vitro and in vivo models of diabetic nephropathy. However, a link between Ang II and SGK-1 in diabetic nephropathy has not been established.

Methods. Ang II production in cultured human proximal tubular cells was measured under normal (5 mM) and high (25 mM) glucose conditions. The Ang II type 1 receptor was identified by RT-PCR. SGK-1 and NHE3 mRNA and protein expression was measured in proximal tubule cells (PTCs) exposed to Ang II. EIPA inhibitable changes in cell sodium uptake were undertaken to confirm that alterations in NHE3 mRNA and protein were reflected in transport activity. SGK-1 was silenced in the PTCs using small interfering RNA to determine the role of SGK-1 in mediating Ang II-induced increases in NHE3-mediated sodium uptake.

Results. Ang II production by PTCs was significantly increased by exposure to high glucose (P <0.02). Ang II increased NHE3 and SGK-1 mRNA expression to 275 +/- 30% (P <0.02) and 130 +/- 10% (P <0.05) respectively. Silencing of SGK-1 reduced Ang II-stimulated NHE3 protein expression to 49.8 +/- 6.1% (P <0.05) of control levels. SGK-1 silencing abolished increases in (22)Na(+) uptake seen in Ang II-treated cells to 86.7 +/- 1.6% of control values.

Conclusion. These data suggest that increased sodium reabsorption in renal proximal tubular cells considered to be due to Ang II in diabetes mellitus is mediated through SGK-1 expression.

Original languageEnglish
Pages (from-to)1834-1843
Number of pages10
JournalNephrology Dialysis Transplantation
Volume23
Issue number6
DOIs
Publication statusPublished - Jun 2008
Externally publishedYes

Keywords

  • angiotensin II
  • diabetes
  • human proximal tubule
  • Na(+)-H(+) exchange
  • SGK-1
  • CONVERTING ENZYME-INHIBITION
  • NA+-H+ EXCHANGE
  • DIABETES-MELLITUS
  • GENE-EXPRESSION
  • RECEPTOR
  • GROWTH
  • TRANSPORT
  • KINASE
  • NEPHROPATHY
  • INSULIN

Cite this

Stevens, V. A., Saad, S., Poronnik, P., Fenton-Lee, C. A., Polhill, T. S., & Pollock, C. A. (2008). The role of SGK-1 in angiotensin II-mediated sodium reabsorption in human proximal tubular cells. Nephrology Dialysis Transplantation, 23(6), 1834-1843. https://doi.org/10.1093/ndt/gfm923