Renal localization and regulation of 15-hydroxyprostaglandin dehydrogenase

Am J Physiol Renal Physiol. 2008 Feb;294(2):F433-9. doi: 10.1152/ajprenal.00436.2007. Epub 2007 Dec 5.


Tissue prostaglandin levels are determined by both biosynthesis and catabolism. The current studies report the expression and localization of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a key enzyme in prostaglandin catabolism in the kidneys. We also investigated potential interactions between 15-PGDH and cyclooxygenase (COX), a key enzyme in prostaglandin biosynthesis. Both 15-PGDH mRNA and protein levels were significantly higher in kidney cortex than in papilla, which is opposite to the expression pattern of COX-2. In situ hybridization indicated that 15-PGDH mRNA was mainly localized to the tubular epithelial cells in kidney cortex and outer medulla but not in the glomerulus or papilla. Dual immunofluorescent staining indicated that 15-PGDH was expressed in the proximal tubule, cortical, and outer medullary thick ascending limb and collecting duct but not in the macula densa or papilla. 15-PGDH levels were significantly lower in a macula densa cell line (MMDD1) than in a proximal tubule cell line. Although a high-salt diet decreased COX-2 expression in macula densa, it increased macula densa 15-PGDH expression in both mouse and rat kidneys. In MMDD1 cells, a COX-2 inhibitor increased 15-PGDH, whereas a COX-1 inhibitor had no effect. Furthermore, intense 15-PGDH immunofluorescent staining was found in both macula densa and glomerulus in COX-2 knockout mice. The intrarenal distribution of 15-PGDH and its interactions with COX-2 suggest that differential regulation of COX-2 and 15-PGDH may play an important role in determining levels of prostaglandins involved in regulation of salt, volume, and blood pressure homeostasis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Cyclooxygenase 2 / metabolism
  • Cyclooxygenase Inhibitors / pharmacology
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Epithelium / drug effects
  • Epithelium / metabolism
  • Gene Expression Regulation, Enzymologic / drug effects
  • Hydroxyprostaglandin Dehydrogenases / genetics
  • Hydroxyprostaglandin Dehydrogenases / metabolism*
  • In Situ Hybridization
  • Kidney / cytology
  • Kidney / drug effects
  • Kidney / metabolism*
  • Kidney Cortex / cytology
  • Kidney Cortex / drug effects
  • Kidney Cortex / metabolism*
  • Kidney Glomerulus / metabolism
  • Kidney Medulla / cytology
  • Kidney Medulla / drug effects
  • Kidney Medulla / metabolism
  • Kidney Tubules, Proximal / cytology
  • Kidney Tubules, Proximal / drug effects
  • Kidney Tubules, Proximal / metabolism
  • Male
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • Organic Chemicals / pharmacology
  • Pyrazoles / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Sodium Chloride, Dietary / pharmacology
  • Sulfonamides / pharmacology
  • Swine


  • 4-(5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide
  • Cyclooxygenase Inhibitors
  • Organic Chemicals
  • Pyrazoles
  • SC 58560
  • Sodium Chloride, Dietary
  • Sulfonamides
  • Hydroxyprostaglandin Dehydrogenases
  • 15-hydroxyprostaglandin dehydrogenase
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2