Antagonistic effects of finerenone and spironolactone on the aldosterone-regulated transcriptome of human kidney cells.
RNA-sequencing
mineralocorticoid
nuclear receptor
steroid hormone
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
02
09
2020
revised:
09
12
2020
accepted:
14
12
2020
entrez:
8
1
2021
pubmed:
9
1
2021
medline:
16
7
2021
Statut:
ppublish
Résumé
Aldosterone, the main mineralocorticoid hormone in humans, plays a pivotal role in the control of water and salt reabsorption via activation of the mineralocorticoid receptor (MR). Alterations in MR signaling pathway lead to renal dysfunction, including chronic kidney disease and renal fibrosis, that can be prevented or treated with mineralocorticoid receptor antagonists (MRAs). Here, we used RNA-Sequencing to analyze effects of two MRAs, spironolactone and finerenone, on the aldosterone-induced transcriptome of a human renal cell line stably expressing the MR. Bioinformatics analysis of the data set reveals the identity of hundreds of genes induced or repressed by aldosterone. Their regulation is modulated in a time-dependent manner and, for the induced genes, depends on the aldosterone-driven direct binding of the MR onto its genomic targets that we have previously characterized. Although both MRAs block aldosterone-induced as well as aldosterone-repressed genes qualitatively similarly, finerenone has a quantitatively more efficient antagonism on some aldosterone-induced genes. Our data provide the first complete transcriptome for aldosterone on a human renal cell line and identifies pro-inflammatory markers (IL6, IL11, CCL7, and CXCL8) as aldosterone-repressed genes.
Identifiants
pubmed: 33417258
doi: 10.1096/fj.202002043RR
doi:
Substances chimiques
Naphthyridines
0
finerenone
0
Spironolactone
27O7W4T232
Aldosterone
4964P6T9RB
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e21314Informations de copyright
© 2021 Federation of American Societies for Experimental Biology.
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