Scientific article
Open access

Expression of claudin-8 is induced by aldosterone in renal collecting duct principal cells

Published inAmerican journal of physiology. Renal physiology., vol. 321, no. 5, p. F645-F655
Publication date2021-11
First online date2021-10-04

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.

  • Aldosterone
  • Claudin
  • Collecting duct
  • Kidney
  • Sodium transport
  • Aldosterone / pharmacology
  • Animals
  • Cell Line
  • Claudins / genetics
  • Claudins / metabolism
  • Diet, Sodium-Restricted
  • Epithelial Sodium Channels / genetics
  • Epithelial Sodium Channels / metabolism
  • Glycogen Synthase Kinase 3 / genetics
  • Glycogen Synthase Kinase 3 / metabolism
  • Kidney Tubules, Collecting / cytology
  • Kidney Tubules, Collecting / drug effects
  • Kidney Tubules, Collecting / metabolism
  • Mice
  • Mineralocorticoid Receptor Antagonists / pharmacology
  • Nucleic Acid Synthesis Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-abl / genetics
  • Proto-Oncogene Proteins c-abl / metabolism
  • Renal Reabsorption / drug effects
  • Sodium / metabolism
  • Sodium, Dietary / toxicity
  • Transcription, Genetic
  • Up-Regulation
  • Src-Family Kinases / genetics
  • Src-Family Kinases / metabolism
Citation (ISO format)
SASSI, Ali et al. Expression of claudin-8 is induced by aldosterone in renal collecting duct principal cells. In: American journal of physiology. Renal physiology., 2021, vol. 321, n° 5, p. F645–F655. doi: 10.1152/ajprenal.00207.2021
Main files (2)
Article (Accepted version)
Article (Published version)
ISSN of the journal1522-1466

Technical informations

Creation10/21/2021 2:05:00 PM
First validation10/21/2021 2:05:00 PM
Update time03/16/2023 2:30:13 AM
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