miR-324-5p and miR-30c-2-3p Alter Renal Mineralocorticoid Receptor Signaling under Hypertonicity
The Mineralocorticoid Receptor (MR) mediates the sodium-retaining action of aldosterone in the distal nephron, but mechanisms regulating MR expression are still poorly understood. We previously showed that RNA Binding Proteins (RBPs) regulate MR expression at the post-transcriptional level in respon...
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| Format: | Article |
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MDPI AG
2022-04-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/9/1377 |
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| author | Thi An Vu Ingrid Lema Imene Hani Lydie Cheval Laura Atger-Lallier Vilayvane Souvannarath Julie Perrot Mélanie Souvanheuane Yannick Marie Sylvie Fabrega Anne Blanchard Jérôme Bouligand Peter Kamenickỷ Gilles Crambert Laetitia Martinerie Marc Lombès Say Viengchareun |
| author_facet | Thi An Vu Ingrid Lema Imene Hani Lydie Cheval Laura Atger-Lallier Vilayvane Souvannarath Julie Perrot Mélanie Souvanheuane Yannick Marie Sylvie Fabrega Anne Blanchard Jérôme Bouligand Peter Kamenickỷ Gilles Crambert Laetitia Martinerie Marc Lombès Say Viengchareun |
| author_sort | Thi An Vu |
| collection | DOAJ |
| description | The Mineralocorticoid Receptor (MR) mediates the sodium-retaining action of aldosterone in the distal nephron, but mechanisms regulating MR expression are still poorly understood. We previously showed that RNA Binding Proteins (RBPs) regulate MR expression at the post-transcriptional level in response to variations of extracellular tonicity. Herein, we highlight a novel regulatory mechanism involving the recruitment of microRNAs (miRNAs) under hypertonicity. RT-qPCR validated miRNAs candidates identified by high throughput screening approaches and transfection of a luciferase reporter construct together with miRNAs Mimics or Inhibitors demonstrated their functional interaction with target transcripts. Overexpression strategies using Mimics or lentivirus revealed the impact on MR expression and signaling in renal KC3AC1 cells. miR-324-5p and miR-30c-2-3p expression are increased under hypertonicity in KC3AC1 cells. These miRNAs directly affect <i>Nr3c2</i> (MR) transcript stability, act with Tis11b to destabilize MR transcript but also repress <i>Elavl1</i> (HuR) transcript, which enhances MR expression and signaling. Overexpression of miR-324-5p and miR-30c-2-3p alter MR expression and signaling in KC3AC1 cells with blunted responses in terms of aldosterone-regulated genes expression. We also confirm that their expression is increased by hypertonicity in vivo in the kidneys of mice treated with furosemide. These findings may have major implications for the pathogenesis of renal dysfunctions, sodium retention, and mineralocorticoid resistance. |
| first_indexed | 2024-03-10T04:17:27Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T04:17:27Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-ea1b4886ea1e4c9f83605f18167a40802023-11-23T07:58:22ZengMDPI AGCells2073-44092022-04-01119137710.3390/cells11091377miR-324-5p and miR-30c-2-3p Alter Renal Mineralocorticoid Receptor Signaling under HypertonicityThi An Vu0Ingrid Lema1Imene Hani2Lydie Cheval3Laura Atger-Lallier4Vilayvane Souvannarath5Julie Perrot6Mélanie Souvanheuane7Yannick Marie8Sylvie Fabrega9Anne Blanchard10Jérôme Bouligand11Peter Kamenickỷ12Gilles Crambert13Laetitia Martinerie14Marc Lombès15Say Viengchareun16Physiologie et Physiopathologie Endocriniennes, Université Paris-Saclay, Inserm, 94276 Le Kremlin-Bicêtre, FrancePhysiologie et Physiopathologie Endocriniennes, Université Paris-Saclay, Inserm, 94276 Le Kremlin-Bicêtre, FrancePhysiologie et Physiopathologie Endocriniennes, Université Paris-Saclay, Inserm, 94276 Le Kremlin-Bicêtre, FranceCentre de Recherche des Cordeliers, Inserm, Sorbonne Université, Université Paris Cité, 75006 Paris, FrancePhysiologie et Physiopathologie Endocriniennes, Université Paris-Saclay, Inserm, 94276 Le Kremlin-Bicêtre, FrancePhysiologie et Physiopathologie Endocriniennes, Université Paris-Saclay, Inserm, 94276 Le Kremlin-Bicêtre, FrancePhysiologie et Physiopathologie Endocriniennes, Université Paris-Saclay, Inserm, 94276 Le Kremlin-Bicêtre, FrancePhysiologie et Physiopathologie Endocriniennes, Université Paris-Saclay, Inserm, 94276 Le Kremlin-Bicêtre, FrancePlateforme de Genotypage Séquençage (iGenSeq), Institut du Cerveau et de la Moelle Epinière, Hôpital Sapêtrière, 75013 Paris, FrancePlateforme Vecteurs Viraux et Transfert de Gènes, Structure Federative de Recherche Necker, UMS 24, UMS 3633, Faculté de Santé, Université Paris Cité, 75015 Paris, FranceInserm, Centre d’Investigations Cliniques 9201, 75015 Paris, FrancePhysiologie et Physiopathologie Endocriniennes, Université Paris-Saclay, Inserm, 94276 Le Kremlin-Bicêtre, FrancePhysiologie et Physiopathologie Endocriniennes, Université Paris-Saclay, Inserm, 94276 Le Kremlin-Bicêtre, FranceCentre de Recherche des Cordeliers, Inserm, Sorbonne Université, Université Paris Cité, 75006 Paris, FrancePhysiologie et Physiopathologie Endocriniennes, Université Paris-Saclay, Inserm, 94276 Le Kremlin-Bicêtre, FrancePhysiologie et Physiopathologie Endocriniennes, Université Paris-Saclay, Inserm, 94276 Le Kremlin-Bicêtre, FrancePhysiologie et Physiopathologie Endocriniennes, Université Paris-Saclay, Inserm, 94276 Le Kremlin-Bicêtre, FranceThe Mineralocorticoid Receptor (MR) mediates the sodium-retaining action of aldosterone in the distal nephron, but mechanisms regulating MR expression are still poorly understood. We previously showed that RNA Binding Proteins (RBPs) regulate MR expression at the post-transcriptional level in response to variations of extracellular tonicity. Herein, we highlight a novel regulatory mechanism involving the recruitment of microRNAs (miRNAs) under hypertonicity. RT-qPCR validated miRNAs candidates identified by high throughput screening approaches and transfection of a luciferase reporter construct together with miRNAs Mimics or Inhibitors demonstrated their functional interaction with target transcripts. Overexpression strategies using Mimics or lentivirus revealed the impact on MR expression and signaling in renal KC3AC1 cells. miR-324-5p and miR-30c-2-3p expression are increased under hypertonicity in KC3AC1 cells. These miRNAs directly affect <i>Nr3c2</i> (MR) transcript stability, act with Tis11b to destabilize MR transcript but also repress <i>Elavl1</i> (HuR) transcript, which enhances MR expression and signaling. Overexpression of miR-324-5p and miR-30c-2-3p alter MR expression and signaling in KC3AC1 cells with blunted responses in terms of aldosterone-regulated genes expression. We also confirm that their expression is increased by hypertonicity in vivo in the kidneys of mice treated with furosemide. These findings may have major implications for the pathogenesis of renal dysfunctions, sodium retention, and mineralocorticoid resistance.https://www.mdpi.com/2073-4409/11/9/1377microRNAsmineralocorticoid receptoraldosteronehypertonicitypost-transcriptional regulationsodium reabsorption |
| spellingShingle | Thi An Vu Ingrid Lema Imene Hani Lydie Cheval Laura Atger-Lallier Vilayvane Souvannarath Julie Perrot Mélanie Souvanheuane Yannick Marie Sylvie Fabrega Anne Blanchard Jérôme Bouligand Peter Kamenickỷ Gilles Crambert Laetitia Martinerie Marc Lombès Say Viengchareun miR-324-5p and miR-30c-2-3p Alter Renal Mineralocorticoid Receptor Signaling under Hypertonicity Cells microRNAs mineralocorticoid receptor aldosterone hypertonicity post-transcriptional regulation sodium reabsorption |
| title | miR-324-5p and miR-30c-2-3p Alter Renal Mineralocorticoid Receptor Signaling under Hypertonicity |
| title_full | miR-324-5p and miR-30c-2-3p Alter Renal Mineralocorticoid Receptor Signaling under Hypertonicity |
| title_fullStr | miR-324-5p and miR-30c-2-3p Alter Renal Mineralocorticoid Receptor Signaling under Hypertonicity |
| title_full_unstemmed | miR-324-5p and miR-30c-2-3p Alter Renal Mineralocorticoid Receptor Signaling under Hypertonicity |
| title_short | miR-324-5p and miR-30c-2-3p Alter Renal Mineralocorticoid Receptor Signaling under Hypertonicity |
| title_sort | mir 324 5p and mir 30c 2 3p alter renal mineralocorticoid receptor signaling under hypertonicity |
| topic | microRNAs mineralocorticoid receptor aldosterone hypertonicity post-transcriptional regulation sodium reabsorption |
| url | https://www.mdpi.com/2073-4409/11/9/1377 |
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