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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:315.)
© 2005 American Heart Association, Inc.

Vascular Biology

Prostaglandin E Synthases in Zebrafish

Barbara Pini; Tilo Grosser; John A. Lawson; Tom S. Price; Michael A. Pack; Garret A. FitzGerald

From the Institute for Translational Medicine and Therapeutics (B.P., T.G., J.A.L., T.S.P., G.A.F.) and the Department of Medicine, Gastroenterology Division (M.A.P.), University of Pennsylvania School of Medicine, Philadelphia.

Correspondence to Garret A. FitzGerald, MD, the Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, 153 Johnson-Pavilion, 3620 Hamilton Walk, Philadelphia, PA 19104-6084. E-mail garret{at}spirit.gcrc.upenn.edu

Objective— Prostaglandin E synthases (PGESs) are being explored as antiinflammtory drug targets as alternatives to cyclooxygenase (COX)-2. Located downstream of the cyclooxygenases, PGESs catalyze PGE₂ formation, and deletion of microsomal (m)-PGES-1 abrogates inflammation. We sought to characterize the developmental expression of COX and PGES in zebrafish.

Methods and Results— We cloned zebrafish cytosolic (c) and m-PGES orthologs and mapped them to syntenic regions of chromosomes 23 and 5. cPGES was widely expressed during development and was coordinately regulated with zCOX-1 in the inner ear, the pronephros, and intestine. COX-2 and mPGES-1 exhibited restricted expression, dominantly in the vasculature of the aortic arch. However, the enzymes were anatomically segregated within the vessel wall. Experiments with antisense morpholinos and with nonsteroidal antiinflammatory drugs suggest that these genes may not be critical for development.

Conclusions— mPGES-1 is developmentally coregulated with COX-2 in vasculature. Given the high fecundidity and translucency of the zebrafish, this model may afford a high throughput system for characterization of novel PGES inhibitors.

Mircosomal prostaglandin E synthase (mPGES)-1, located downstream of COX-2, may represent a novel antiinflammatory drug target. Zebrafish cytosolic (c) PGES-1 and COX-1 were coordinately expressed; mPGES-1 and COX-2 were expressed particularly in the vasculature. Zebrafish may afford a high throughput system for detection of novel PGES inhibitors.

Key Words: prostaglandin E synthase • cyclooxygenase • zebrafish • Danio rerio • vascular biology

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