Antagonistic effects of finerenone and spironolactone on the aldosterone‐regulated transcriptome of human kidney cells - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue FASEB Journal Année : 2021

Antagonistic effects of finerenone and spironolactone on the aldosterone‐regulated transcriptome of human kidney cells

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.
Fichier sous embargo
Fichier sous embargo
Date de visibilité indéterminée

Dates et versions

inserm-03483685 , version 1 (16-12-2021)

Identifiants

Citer

Florian Le Billan, Julie Perrot, Elena Carceller, Simon Travers, Say Viengchareun, et al.. Antagonistic effects of finerenone and spironolactone on the aldosterone‐regulated transcriptome of human kidney cells. FASEB Journal, 2021, 35 (2), pp.e21314. ⟨10.1096/fj.202002043RR⟩. ⟨inserm-03483685⟩
16 Consultations
5 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More