ECEESPE2025 Poster Presentations Fetal and Neonatal Endocrinology (15 abstracts)
Deciphering the physiological downregulation of mineralocorticoid receptor expression at birth: implications of mir-409-3p and mir-431-5p
Martinerie Laetitia 1 , Imene Hani 2 , Laurent Guyon 3 , Nadia Cherradi 4 , Thi An Vu 2 , Julie Perrot 2 , Thivya Rajkumar 2 , Eric Pussard 5 , Pascal Boileau 6 , Riwan Riwan 7 , Justine Guegan 7 , Jérôme Bouligand 5 , Peter Kamenicky 8 , Marc Lombès 2 & Say Viengchareun 2
1Endocrinologie Pédiatrique, Centre de Référence Maladies Endocriniennes Rares de la Croissance et du Développement, Hôpital Universitaire Robert-Debré APHP Nord, Paris 75019, France, Université Paris-Cité, Faculté de Santé, UFR de Médecine, Paris 75005, France, PARIS, France; 2Université Paris-Saclay, Inserm, Physiologie et Physiopathologie Endocriniennes, 94276 Le Kremlin-Bicêtre, France, Le Kremlin-Bicêtre, France; 3Inserm U1292, CEA, UGA, 38054, Grenoble, France; 4Inserm U1292, CEA, UGA, 38054, Grenoble, France, Grenoble, France; 5Service de Génétique Moléculaire, Pharmacogénétique et Hormonologie, Hôpital Bicêtre APHP Paris Saclay, Le Kremlin Bicêtre 94270, France, Le Kremlin-Bicêtre, France; 6Department of Neonatal Pediatrics, Poissy Saint Germain Hospital, Versailles Saint Quentin en Yvelines University, Poissy, France, Poissy, France; 7Institut du Cerveau, Hôpital de la Pitié-Salpêtrière, 47 boulevard de l’Hôpital, 75646, Paris, France, Paris, France; 8Service d’Endocrinologie et des Maladies de la Reproduction, Hôpital Bicêtre APHP Paris Saclay, Le Kremlin-Bicêtre 94270, France, Le Kremlin-Bicêtre, France.
JOINT3850
Aldosterone regulates sodium homeostasis by binding to the Mineralocorticoid Receptor (MR). We have previously identified a critical temporal window during renal development with a down regulation of MR expression at birth, explaining the physiological sodium losses observed in newborns. However, the molecular mechanisms governing MR expression remain unclear. Here, we report the involvement of two microRNAs (miRNAs), miR-409-3p and miR-431-5p, in regulating MR expression during early renal development. Using miRNA sequencing, we identified these miRNAs as upregulated on mouse postnatal day 0 (D0) compared to day 8 (D8). RT-qPCR validated their differential expression, while luciferase reporter assays confirmed their functional interaction with MR transcripts. Functional studies using miRNA mimics and inhibitors revealed that miR-409-3p and miR-431-5p modulate MR expression and signaling in primary renal cell cultures. Specifically, their increased expression at D0 destabilizes MR transcripts and decreases MR expression and signaling, while their decreased expression at D8 leads to MR stabilization and enhanced mineralocorticoid signaling. Notably, digital droplet PCR (ddPCR) analysis of neonatal urine samples from the PREMALDO cohort demonstrated that these miRNAs are highly expressed at birth in humans but decrease gradually postnatally. Our findings identify miR-409-3p and miR-431-5p as key regulators of MR expression and mineralocorticoid signaling during renal development. These miRNAs could serve as potential predictive and non-invasive biomarkers of renal maturity and mineralocorticoid signaling efficiency notably in premature infants that have exacerbated sodium losses due to mineralocorticoid signaling defect in the neonatal period.
Volume 110
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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