Expression of claudin-8 is induced by aldosterone in renal collecting duct principal cells
Autor: | Valérie Olivier, Isabelle Roth, Khalil Udwan, Alexandra Chassot, Olivier Staub, Yubao Wang, Suresh Ramakrishnan, Eric Féraille, Ali Sassi |
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Rok vydání: | 2021 |
Předmět: |
Collecting duct
Pathology Transcription Genetic Physiology 030232 urology & nephrology Kidney Kidney Tubules Collecting / drug effects Sodium transport chemistry.chemical_compound Glycogen Synthase Kinase 3 Mice 0302 clinical medicine Sodium / metabolism Src-Family Kinases / metabolism Proto-Oncogene Proteins c-abl Aldosterone Mineralocorticoid Receptor Antagonists 0303 health sciences Claudins / metabolism Diet Sodium-Restricted Up-Regulation medicine.anatomical_structure src-Family Kinases Sodium Dietary / toxicity medicine.medical_specialty Claudins / genetics Glycogen Synthase Kinase 3 / genetics Cell Line 03 medical and health sciences Downregulation and upregulation Kidney Tubules Collecting / metabolism medicine Nucleic Acid Synthesis Inhibitors / pharmacology Animals Kidney Tubules Collecting Claudin ddc:612 Renal Reabsorption / drug effects Epithelial Sodium Channels Mineralocorticoid Receptor Antagonists / pharmacology 030304 developmental biology Nucleic Acid Synthesis Inhibitors Src-Family Kinases / genetics urogenital system Epithelial Sodium Channels / genetics Epithelial Sodium Channels / metabolism Sodium Sodium Dietary Proto-Oncogene Proteins c-abl / metabolism Renal Reabsorption Aldosterone / pharmacology chemistry Kidney Tubules Collecting / cytology Claudins Mouse Kidney Proto-Oncogene Proteins c-abl / genetics Glycogen Synthase Kinase 3 / metabolism Duct (anatomy) |
Zdroj: | American journal of physiology. Renal physiology., Vol. 321, No 5 (2021) pp. F645-F655 |
ISSN: | 1522-1466 |
Popis: | Fine tuning of Na + reabsorption takes place along the aldosterone-sensitive distal nephron (ASDN) which includes the collecting duct (CD) where it is mainly regulated by aldosterone. In the CD,Na + reabsorption is mediated by the epithelial sodium channel (ENaC) and the sodium pump (Na,K-ATPase). Paracellular ion permeability is mainly dependent on tight junction permeability. Claudin-8 is one of the main tight-junction proteins expressed along the ASDN. We have previously shown a coupling between trancellular Na + reabsorption and paracellular Na + barrier. We hypothesize that aldosterone controls the expression levels of both transcellular Na + transporters and paracellular claudin-8 in a coordinated manner. Here, we show that aldosterone increased mRNA and protein levels as well as lateral membrane localization of claudin-8 in cultured CD principal cells. The increase in claudin-8 mRNA levels in response to aldosterone was prevented by preincubation with 17-hydroxy progesterone, a mineralocorticoid receptor antagonist, and by inhibition of transcription with actinomycin D. We also show that low salt diet which stimulated aldosterone secretion was associated with increased claudin-8 abundance in the mouse kidney. Reciprocally, mice subjected to high salt diet which inhibits aldosterone secretion or treated with spironolactone, a mineralocorticoid receptor (MR)antagonist, displayed decreased claudin-8 expression. Inhibition of glycogen synthase kinase-3 (GSK3), Lyn and Abl signaling pathways prevented the effect of aldosterone on claudin-8 mRNA and protein abundance, suggesting that signaling protein kinases plays a permissive role on the transcriptional activity of the mineralocorticoid receptor.This study shows that signaling via multiple protein kinases working in concert mediates the aldosterone-induced claudin-8 expression in collecting duct. |
Databáze: | OpenAIRE |
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