Aldosterone regulates a 5' variant sgk1 transcript via a shared hormone response element in the sgk1 5' regulatory region

Nandita S Raikwar; Christie P Thomas

doi:10.14814/phy2.13221

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Aldosterone regulates a 5' variant sgk1 transcript via a shared hormone response element in the sgk1 5' regulatory region

Journal article

Open access

Peer reviewed

Aldosterone regulates a 5' variant sgk1 transcript via a shared hormone response element in the sgk1 5' regulatory region

Nandita S Raikwar and Christie P Thomas

Physiological reports, Vol.5(7), pp.e13221-n/a

04/2017

DOI: 10.14814/phy2.13221

PMCID: PMC5392512

PMID: 28408636

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https://doi.org/10.14814/phy2.13221View

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Abstract

We previously identified a 5' variant alternate transcript of Sgk1 (Sgk1_v3) encoding an NH -terminal variant Sgk1 isoform, Sgk1_i3 that, like Sgk1, is expressed in the distal convoluted tubule, connecting tubule and collecting duct and can stimulate epithelial Na transport (Am J Physiol Renal Physiol 303: F1527-F1533, 2012). We now demonstrate that, similar to Sgk1, aldosterone and glucocorticoids stimulate Sgk1_v3 expression in cell lines from the collecting duct and airway epithelia. In mice, short term aldosterone infusion and maneuvers that increase endogenous aldosterone secretion including dietary Na deprivation and K loading increases distal nephron Sgk1_v3 expression in vivo. Although Sgk1_v3 has a different 5' proximal regulatory region from Sgk1, the transcription start sites are less than 1000 bp apart. We cloned the 5' regulatory region for Sgk1 and Sgk_v3 upstream of a luciferase gene and by deletion and reporter gene analysis we localized the corticosteroid regulatory region for Sgk1_v3 to a glucocorticoid response element (GRE) that had previously been identified for Sgk1 (Am J Physiol Endo Metab 283: E971-E979, 2002). We tested this element with MR in an MR-null cell line and demonstrate that aldosterone stimulates Sgk1 and Sgk1_v3 via this GRE We conclude that corticosteroids stimulate Sgk1 and Sgk1_v3 expression in epithelial cells via activation of a common conserved GRE in the 5' flanking region of Sgk1.

Potassium - metabolism

Response Elements

Humans

Mice, Inbred C57BL

RNA, Messenger - genetics

Transcriptional Activation

Protein-Serine-Threonine Kinases - genetics

Sodium - metabolism

RNA, Messenger - metabolism

Immediate-Early Proteins - metabolism

Aldosterone - metabolism

Animals

Immediate-Early Proteins - genetics

Glucocorticoids - metabolism

HEK293 Cells

Cell Line, Tumor

5' Flanking Region

Mice

Respiratory Mucosa - metabolism

Nephrons - metabolism

Protein-Serine-Threonine Kinases - metabolism

Details

Title: Subtitle: Aldosterone regulates a 5' variant sgk1 transcript via a shared hormone response element in the sgk1 5' regulatory region
Creators: Nandita S Raikwar - Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa
Christie P Thomas - The Veterans Affairs Medical Center, Iowa City, Iowa
Resource Type: Journal article
Publication Details: Physiological reports, Vol.5(7), pp.e13221-n/a
DOI: 10.14814/phy2.13221
PMID: 28408636
PMCID: PMC5392512
NLM abbreviation: Physiol Rep
ISSN: 2051-817X
eISSN: 2051-817X
Publisher: United States
Grant note: R01 DK090053 / NIDDK NIH HHS R01 HL071664 / NHLBI NIH HHS
Language: English
Date published: 04/2017
Academic Unit: Stead Family Department of Pediatrics; Obstetrics and Gynecology; Internal Medicine
Record Identifier: 9983985903802771

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