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

doi:10.1093/ndt/gfm923

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 journal › Article › peer-review

36 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 language	English
Pages (from-to)	1834-1843
Number of pages	10
Journal	Nephrology Dialysis Transplantation
Volume	23
Issue number	6
DOIs	https://doi.org/10.1093/ndt/gfm923
Publication status	Published - Jun 2008
Externally published	Yes

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

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10.1093/ndt/gfm923

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@article{2b20990d80b04dbc8e64d1b56d407b10,

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

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.",

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",

author = "Stevens, {Veronica A.} and Sonia Saad and Philip Poronnik and Fenton-Lee, {Carol A.} and Polhill, {Tania S.} and Pollock, {Carol A.}",

year = "2008",

month = jun,

doi = "10.1093/ndt/gfm923",

language = "English",

volume = "23",

pages = "1834--1843",

journal = "Nephrology Dialysis Transplantation",

issn = "0931-0509",

publisher = "OXFORD UNIV PRESS INC",

number = "6",

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T1 - The role of SGK-1 in angiotensin II-mediated sodium reabsorption in human proximal tubular cells

AU - Stevens, Veronica A.

AU - Saad, Sonia

AU - Poronnik, Philip

AU - Fenton-Lee, Carol A.

AU - Polhill, Tania S.

AU - Pollock, Carol A.

PY - 2008/6

Y1 - 2008/6

N2 - 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.

AB - 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.

KW - angiotensin II

KW - diabetes

KW - human proximal tubule

KW - Na(+)-H(+) exchange

KW - SGK-1

KW - CONVERTING ENZYME-INHIBITION

KW - NA+-H+ EXCHANGE

KW - DIABETES-MELLITUS

KW - GENE-EXPRESSION

KW - RECEPTOR

KW - GROWTH

KW - TRANSPORT

KW - KINASE

KW - NEPHROPATHY

KW - INSULIN

U2 - 10.1093/ndt/gfm923

DO - 10.1093/ndt/gfm923

M3 - Article

C2 - 18238849

SN - 0931-0509

VL - 23

SP - 1834

EP - 1843

JO - Nephrology Dialysis Transplantation

JF - Nephrology Dialysis Transplantation

IS - 6

ER -

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

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Keywords

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