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
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