Membrane-associated PGE synthase-1 (mPGES-1) is coexpressed with both COX-1 and COX-2 in the kidney.

Schneider A, Zhang Y, Zhang M, Lu WJ, Rao R, Fan X, Redha R, Davis L, Breyer RM, Harris R, Guan Y, Breyer MD
Kidney Int. 2004 65 (4): 1205-13

PMID: 15086459 · DOI:10.1111/j.1523-1755.2004.00493.x

BACKGROUND - Prostaglandin E2 (PGE2) plays an important role in many physiologic and pathophysiologic processes in the kidney. Multiple enzymes are involved in PGE2 biosynthesis, including phospholipases, cyclooxygenases (COX), and the PGE2 synthases (PGES). The present studies were aimed at determining the intrarenal localization of mPGES-1 and whether it is coexpressed with COX-1 or COX-2.

METHODS - Rabbit mPGES-1 and COX-1 cDNAs were cloned using reverse transcription-polymerase chain reaction (RT-PCR) and screening a cDNA library. RNase protection assay and immunoblotting were used to examine mPGES-1 expression levels. In situ hybridization and immunostaining were used to determine the intrarenal localization of mPGES-1 and cyclooxygenases.

RESULTS - Rabbit mPGES-1 shares high sequence similarity to the human homolog. Nuclease protection studies showed that the kidney expresses among the highest level of mPGES-1 of any rabbit tissue. In situ hybridization showed COX-1 and mPGES-1 mRNA was highly expressed in renal medullary collecting ducts (MCD), and to a lesser extent in cortical collecting ducts (CCD). Fainter mPGES-1 expression was also observed in macula densa (MD) and medullary interstitial cells (RMICs), where COX-2 is highly expressed. Double-labeling studies (immunostaining plus in situ hybridization) and immunohistochemistry of mouse tissues confirmed that mPGES-1 predominantly colocalizes with COX-1 in distal convoluted tubule (DCT), CCD, and MCD, and is coexpressed with COX-2 at lower levels in MD and RMICs.

CONCLUSION - Together, these studies suggest mPGES-1 colocalizes with both COX-1 and COX-2 to mediate the biosynthesis of PGE2 in the kidney.

MeSH Terms (21)

Amino Acid Sequence Animals Base Sequence Cell Membrane Cloning, Molecular Cyclooxygenase 1 Cyclooxygenase 2 DNA, Complementary Female Intramolecular Oxidoreductases Isoenzymes Kidney Kidney Medulla Kidney Tubules, Collecting Membrane Proteins Mice Molecular Sequence Data Prostaglandin-Endoperoxide Synthases Rabbits RNA, Messenger Tissue Distribution

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