Dietary salt induces transcription of the prostaglandin transporter gene in renal collecting ducts.
Prostaglandin E(2) (PGE(2)) plays an important role in maintaining body fluid homeostasis by activating its receptors on the renal collecting duct (CD) to stimulate renal Na(+) and water excretion. The PG carrier prostaglandin transporter (PGT) is expressed on the CD apical membrane, where it mediates PG reuptake as part of the termination of autocrine PG signaling. Here we tested the hypothesis that dietary salt loading regulates PGT gene transcription in renal CDs. We placed green fluorescence protein (GFP) under control of 3.3 kb of the mouse PGT promoter and injected this construct into the pronuclei of fertilized FVB mouse eggs. Four of thirty-eight offspring were GFP positive by genotyping. We extensively characterized one (no. 29) PGT-GFP transgenic mouse line. On microscopic examination, GFP was expressed in CDs as determined by their expression of aquaporin-2. We fed mice a low (0.03% NaCl)-, normal (0.3% NaCl)-, or high-salt (3% NaCl) diet for 2 wk and quantified CD GFP expression. The average number of GFP-positive CD cells per microscopic section varied directly with dietary salt intake. Compared with mice on the control (0.3% sodium) diet, mice on a low-sodium (0.03%) diet had reduced numbers of GFP-positive cells (71% of control, P < 0.001), whereas mice on a high-sodium (3%) diet had increased numbers of GFP-positive cells (139% of control, P < 0.001). This increase in apparent CD PGT transcription resulted in a 51-55% increase (P < 0.001) in whole kidney PGT mRNA levels as determined by real-time PCR. The regulation of PG signal termination via reuptake represents a new pathway for controlling renal Na(+) balance.
Chi
Yuling
Y
Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Pucci
Michael L
ML
Schuster
Victor L
VL
D000818:Animals; D001947:Breeding; D015245:Deoxyribonuclease BamHI / Q000378:metabolism; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D018628:Gene Dosage; D017930:Genes, Reporter; D005838:Genotype; D049452:Green Fluorescent Proteins / Q000235:genetics; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D027361:Organic Anion Transporters / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects*; D019076:Transgenes
D027361:Organic Anion Transporters; C503527:Slco2a1 protein, mouse; D017673:Sodium Chloride, Dietary; D049452:Green Fluorescent Proteins; D015245:Deoxyribonuclease BamHI; C074326:CTTAAG-specific type II deoxyribonucleases; D015252:Deoxyribonucleases, Type II Site-Specific