Early transcriptional effects of aldosterone in a mouse inner medullary  collecting duct cell line

Gumz, Michelle L.; Popp, Michael P.; Wingo, Charles S.; Cain, Brian D.

doi:10.1152/ajprenal.00353.2002

Cited by 110 publications

(105 citation statements)

References 38 publications

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“…Consistent with previously reported data (19), inhibition of MR or GR with spironolactone or RU486, respectively, completely blocked aldosterone induction of edn1 mRNA (Fig. 4A).…”

Section: Aldosterone Stimulates Et-1 Insupporting

confidence: 93%

“…Previously, we identified endothelin-1 (edn1) as a transcript and protein that increases in response to aldosterone in inner medullary collecting duct (mIMCD-3) cells (19). Similarly, this interaction has been documented in whole kidney extracts from rat (20).…”

mentioning

confidence: 74%

“…Indeed, our original report showed stimulation of edn1 mRNA by aldosterone occurred in mIMCD-3 cells (19). To determine if collecting duct cells were also the target cell type in the animal, aldosterone studies were conducted on acutely isolated rat IMCD cells ex vivo.…”

Section: Aldosterone Stimulates Et-1 Inmentioning

confidence: 99%

“…Previously, we identified endothelin-1 (edn1) as a transcript and protein that increases in response to aldosterone in inner medullary collecting duct (mIMCD-3) cells (19). Similarly, this * This work was supported, in whole or in part, by National Institutes of Health Grant RO1-DK049750 (to C. S. W.) from USPHS.…”

mentioning

confidence: 92%

“…MR and GR share 94% homology in their DNA binding domains and have conserved amino acids at each residue shown to make direct contacts with DNA (1, 12). Indeed, MR and GR are known to bind to the same HRE in several genes (13)(14)(15)(16)(17)(18).Previously, we identified endothelin-1 (edn1) as a transcript and protein that increases in response to aldosterone in inner medullary collecting duct (mIMCD-3) cells (19). Similarly, this * This work was supported, in whole or in part, by National Institutes of Health Grant RO1-DK049750 (to C. S. W.) from USPHS.…”

mentioning

confidence: 99%

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Aldosterone Modulates Steroid Receptor Binding to the Endothelin-1 Gene (edn1)

Stow

Gumz

Lynch

et al. 2009

Journal of Biological Chemistry

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Aldosterone and endothelin-1 (ET-1) act on collecting duct cells of the kidney and are important regulators of renal sodium transport and cardiovascular physiology. We recently identified the ET-1 gene (edn1) as a novel aldosterone-induced transcript. However, aldosterone action on edn1 has not been characterized at the present time. In this report, we show that aldosterone stimulated edn1 mRNA in acutely isolated rat inner medullary collecting duct cells ex vivo and ET-1 peptide in rat inner medulla in vivo. Aldosterone induction of edn1 mRNA occurred in cortical, outer medullary, and inner medullary collecting duct cells in vitro. Inspection of the edn1 promoter revealed two putative hormone response elements. Levels of heterogeneous nuclear RNA synthesis demonstrated that edn1 mRNA stimulation occurred at the level of transcription. RNA knockdowns corroborated pharmacological studies and demonstrated both mineralocorticoid receptor and glucocorticoid receptor participated in this response. Aldosterone resulted in dose-dependent nuclear translocation and binding of mineralocorticoid receptor and glucocorticoid receptor to the edn1 hormone response elements. Hormone receptors mediated the association of chromatin remodeling complexes, histone modification, and RNA polymerase II at the edn1 promoter. Direct interaction between aldosterone and ET-1 has important implications for renal and cardiovascular function.The steroid hormone aldosterone is critical for sodium homeostasis and blood pressure control. Aldosterone works by modulating the fine regulation of sodium reabsorption in the distal nephron and collecting duct of the kidney. Classic aldosterone action is mediated through the mineralocorticoid receptor (MR), 3 a member of the nuclear receptor family of proteins that function as ligand-dependent transcription factors (1). MR acts on cells of the distal nephron and collecting duct to stimulate transcription of genes involved in transepithelial sodium transport, including the epithelial sodium channel ␣ subunit (scnn1a, ␣ENaC), the sodium, potassium-ATPase ␣1 subunit (atp1a1), and the serum-and glucocorticoid-regulated kinase-1 (sgk1) (2). The increase in expression of genes involved in sodium transport results in net sodium reabsorption followed by in increase in extracellular fluid volume and a consequent increase in blood pressure. Indeed, MR antagonists such as spironolactone and eplerenone are used clinically as diuretic and anti-hypertensive agents (3). The mechanism of MR action is consistent with a classic steroid receptor mechanism (4). Prior to activation MR resides in the cytosol. Ligand binding induces a conformational change that releases chaperone proteins and reveals a nuclear localization signal. Nuclear MR binds directly to DNA at hormone response elements (HREs) in target genes to modulate their transcription. A typical HRE for MR consists of two receptor binding half-sites with the consensus sequence 5Ј-TGTTCT-3Ј, arranged as an inverted palindrome (1, 5). These HREs facilitate binding of...

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“…Consistent with previously reported data (19), inhibition of MR or GR with spironolactone or RU486, respectively, completely blocked aldosterone induction of edn1 mRNA (Fig. 4A).…”

Section: Aldosterone Stimulates Et-1 Insupporting

confidence: 93%

mentioning

confidence: 74%

Section: Aldosterone Stimulates Et-1 Inmentioning

confidence: 99%

“…Previously, we identified endothelin-1 (edn1) as a transcript and protein that increases in response to aldosterone in inner medullary collecting duct (mIMCD-3) cells (19). Similarly, this * This work was supported, in whole or in part, by National Institutes of Health Grant RO1-DK049750 (to C. S. W.) from USPHS.…”

mentioning

confidence: 92%

mentioning

confidence: 99%

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Aldosterone Modulates Steroid Receptor Binding to the Endothelin-1 Gene (edn1)

Stow

Gumz

Lynch

et al. 2009

Journal of Biological Chemistry

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Identification of early-responsive genes correlated to valproic acid-induced neural tube defects in mice

et al. 2005

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BACKGROUND:Valproic acid (VPA) causes the failure of neural tube closure in newborn mice. However, the molecular mechanism of its teratogenesis is unknown. This study was conducted to investigate the genomewide effects of VPA disruption of normal neural tube development in mice. METHODS: Microarray analysis was performed on the head part of NMRI mouse embryos treated for 1 hr with VPA on gestational day (GD) 8. Subsequently, we attempted to isolate genes that changed in correlation with the teratogenic action of VPA by employing reduced teratogenic VPA analogs, valpromide (VPD) and valnoctamide (VCD), in a real-time PCR study. RESULTS: Microarray results demonstrated that during neurulation, many genes, some of whose functions are known and some unknown, were either increased or decreased after VPA injection. Some genes were affected by VPD or VCD in the same way as VPA, but others were not changed by the analogs. In this way, our system identified 11 increased and 20 decreased genes. Annotation analysis revealed that the increased genes included gadd45b, ier5, per1, phfl3, pou3f1, and sox4, and the decreased genes included ccne2, ccnl, gas5, egr2, sirt1, and zfp105. CONCLUSIONS: These findings demonstrate that expression changes in genes having roles in the cell cycle and apoptosis pathways of neural tube cells were strongly expected to relate to the teratogenic, but not antiepileptic, activity of VPA. Our approach has allowed the expansion of the catalog of molecules immediately affected by VPA in the developing neural tube.

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Physiology of Endothelin and the Kidney

Kohan

Inscho

Wesson

et al. 2011

Comprehensive Physiology

101

136

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Since its discovery in 1988 as an endothelial cell-derived peptide that exerts the most potent vasoconstriction of any known endogenous compound, endothelin (ET) has emerged as an important regulator of renal physiology and pathophysiology. This review focuses on how the ET system impacts renal function in health; it is apparent that ET regulates multiple aspects of kidney function. These include modulation of glomerular filtration rate and renal blood flow, control of renin release, and regulation of transport of sodium, water, protons and bicarbonate. These effects are exerted through ET interactions with almost every cell type in the kidney, including mesangial cells, podocytes, endothelium, vascular smooth muscle, every section of the nephron, and renal nerves. In addition, while not the subject of the current review, ET can also indirectly affect renal function through modulation of extrarenal systems, including the vasculature, nervous system, adrenal gland, circulating hormones and the heart. As will become apparent, these pleiotropic effects of ET are of fundamental physiologic importance in the control of renal function in health. In addition, to help put these effects into perspective, we will also discuss, albeit to a relatively limited extent, how alterations in the ET system can contribute to hypertension and kidney disease.

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Early transcriptional effects of aldosterone in a mouse inner medullary collecting duct cell line

Cited by 110 publications

References 38 publications

Aldosterone Modulates Steroid Receptor Binding to the Endothelin-1 Gene (edn1)

Aldosterone Modulates Steroid Receptor Binding to the Endothelin-1 Gene (edn1)

Identification of early-responsive genes correlated to valproic acid-induced neural tube defects in mice

Physiology of Endothelin and the Kidney

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