Cloning, expression, and regulation of rabbit cyclooxygenase-2 in renal medullary interstitial cells

Youfei Guan, Min Chang, Wonyong Cho, Yahua Zhang, Reyadh Redha, Linda Davis, Sam Chang, Raymond N. Dubois, Chuan Ming Hao, Matthew Breyer

    Research output: Contribution to journalArticle

    156 Scopus citations

    Abstract

    Prostaglandin synthesis requires cyclooxygenase-1 (COX1) or -2 (COX2), which mediate the conversion of arachidonate to prostaglandin H2. COX1 is the predominant constitutive isoform, whereas COX2 expression is typically low. In the present studies we cloned rabbit COX2 and determined its distribution in unstimulated tissues. Screening rabbit eye and uterine libraries yielded two cDNAs containing identical inserts with a 1,812- nucleotide open-reading frame. This encoded a 604-amino acid polypeptide, 90% identical to human, rat, and mouse COX2. Expression of the rabbit COX2 in HEK-293 cells enhanced prostanoid synthesis. Constitutive COX2 mRNA expression was highest in kidney and urinary bladder. COX2 expression was primarily in renal outer medullary interstitial cells with cortical expression in macula densa. In cultured medullary interstitial cells, COX2 mRNA predominated, with little COX1 expression. Interstitial cell COX2 mRNA but not COX1 was induced by phorbol ester and epidermal growth factor but suppressed by dexamethasone. Phorbol ester also upregulated immunoreactive COX2. Constitutive COX2 in these tissues has important implications for side effects of COX2-selective inhibitors.

    Original languageEnglish (US)
    Pages (from-to)F18-F26
    JournalAmerican Journal of Physiology - Renal Physiology
    Volume273
    Issue number1 42-1
    DOIs
    StatePublished - Jul 1997

    Keywords

    • Epidermal growth factor
    • Eye
    • Phorbol 12-myristate 13- acetate
    • Prostaglandin synthase

    ASJC Scopus subject areas

    • Physiology
    • Urology

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  • Cite this

    Guan, Y., Chang, M., Cho, W., Zhang, Y., Redha, R., Davis, L., Chang, S., Dubois, R. N., Hao, C. M., & Breyer, M. (1997). Cloning, expression, and regulation of rabbit cyclooxygenase-2 in renal medullary interstitial cells. American Journal of Physiology - Renal Physiology, 273(1 42-1), F18-F26. https://doi.org/10.1152/ajprenal.1997.273.1.f18