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Published on: September 26, 2018
A direct effect of aldosterone on endothelin-1 gene expression in vivo
Stephen Wong1, Francine E Brennan, Morag J Young
1Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.
Abstract:
Aldosterone regulates sodium reabsorption in epithelial tissues such as the kidney and colon, via a pathway involving the activation of intracellular mineralocorticoid receptors (MR), induction of specific target genes, and a subsequent increase in sodium channel activity. Characterized aldosterone target genes in epithelia include the serum and glucocorticoid-regulated kinase 1 and the corticosteroid hormone-induced factor. Endothelin-1 (ET-1) is a potent vasoconstrictor that alters both sodium transport and hydrogen ion secretion in the kidney. Recent studies in a mouse medullary collecting duct cell line and rat A-10 smooth muscle cells have demonstrated an acute response of ET-1 gene expression to aldosterone. In the present study, we have investigated the ET-1 gene in vivo as a potential direct aldosterone-regulated target gene in the kidney and colon. Adrenalectomized rats given a single dose of aldosterone were found to have a 2-fold increase in ET-1 mRNA levels in the kidney and colon after 1 h. No significant changes in mRNA levels were detected for the related isoforms ET-2 or ET-3. Cotreatment with aldosterone and potassium canrenoate, a MR antagonist, blocked induction of ET-1 mRNA, suggesting that induction was mediated via the MR. In a time course study, ET-1 mRNA levels were induced rapidly by aldosterone, with levels of ET-1 mRNA maximally increased 2- and 2.5-fold after 1 h in the kidney and colon, respectively. These results suggest that ET-1 is a direct aldosterone gene target in the kidney and colon and may play an important role in aldosterone-regulated ion homeostasis.
Insights
Endothelin-1 (ET-1) is a direct aldosterone target gene in the kidney and colon. Aldosterone rapidly increases ET-1 mRNA levels, suggesting its role in regulating ion homeostasis.
Area of Science:
- Endocrinology
- Molecular Biology
- Physiology
Background:
- Aldosterone is a key hormone regulating sodium reabsorption in epithelial tissues like the kidney and colon.
- This process involves mineralocorticoid receptor (MR) activation, gene induction, and increased sodium channel activity.
- Endothelin-1 (ET-1), a vasoconstrictor, influences kidney sodium and hydrogen ion transport.
Purpose of the Study:
- To investigate Endothelin-1 (ET-1) as a direct aldosterone-regulated target gene in vivo.
- To determine the role of the mineralocorticoid receptor (MR) in ET-1 gene regulation by aldosterone.
Main Methods:
- Adrenalectomized rats were administered aldosterone and/or a MR antagonist (potassium canrenoate).
- Quantitative real-time PCR was used to measure ET-1 mRNA levels in kidney and colon tissues.
- Time course experiments assessed the rapid induction of ET-1 mRNA following aldosterone administration.
Main Results:
- A single dose of aldosterone increased ET-1 mRNA levels 2-fold in the kidney and colon after 1 hour.
- Aldosterone did not significantly affect mRNA levels of related isoforms ET-2 or ET-3.
- Co-administration of aldosterone and a MR antagonist blocked ET-1 mRNA induction, confirming MR mediation.
- ET-1 mRNA levels peaked at 2- and 2.5-fold increases in the kidney and colon, respectively, within 1 hour.
Conclusions:
- Endothelin-1 (ET-1) is a direct aldosterone-induced gene target in the kidney and colon.
- The mineralocorticoid receptor (MR) mediates aldosterone's effect on ET-1 gene expression.
- ET-1 may play a significant role in aldosterone-mediated ion homeostasis.
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