PGE2 EP3 receptor downregulates COX-2 expression in the medullary thick ascending limb induced by hypertonic NACl

Shoujin Hao, Alejandra Hernandez, Mariana Quiroz-Munoz, Carlos Cespedes, Carlos P. Vio, Nicholas R. Ferreri*

*Autor correspondiente de este trabajo

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

11 Citas (Scopus)

Resumen

We tested the hypothesis that inhibition of EP3 receptors enhances cyclooxygenase (COX)-2 expression in the thick ascending limb (TAL) induced by hypertonic stimuli. COX-2 protein expression in the outer medulla increased approximately twofold in mice given free access to 1% NaCl in the drinking water for 3 days. The increase was associated with an approximate threefold elevation in COX-2 mRNA accumulation and an increase in PGE2 production by isolated medullary (m)TAL tubules from 77.3 ± 8.4 to 165.7 [1] 10.8 pg/mg protein. Moreover, administration of NS-398 abolished the increase in PGE2 production induced by 1% NaCl. EP3 receptor mRNA levels also increased approximately twofold in the outer medulla of mice that ingested 1% NaCl. The selective EP3 receptor antagonist L-798106 increased COX-2 mRNA by twofold in mTAL tubules, and the elevation in COX-2 protein induced by 1% NaCl increased an additional 50% in mice given L-798106. COX-2 mRNA in primary mTAL cells increased twofold in response to media made hypertonic by the addition of NaCl (400 mosmol/kg H2O). L-798106 increased COX-2 mRNA twofold in isotonic media and fourfold in cells exposed to 400 mosmol/kg H2O. PGE2 production by mTAL cells increased from 79.3 ± 4.6 to 286.7 ± 6.3 pg/mg protein after challenge with 400 mosmol/kg H2O and was inhibited in cells transiently transfected with a lentivirus short hairpin RNA construct targeting exon 5 of COX-2 to silence COX-2. Collectively, the data suggest that local hypertonicity in the mTAL is associated with an increase in COX-2 expression concomitant with elevated EP3 receptor expression, which limits COX-2 activity in this segment of the nephron.

Idioma originalInglés
Páginas (desde-hasta)F736-F746
PublicaciónAmerican Journal of Physiology - Renal Physiology
Volumen307
N.º6
DOI
EstadoPublicada - 2014
Publicado de forma externa

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Publisher Copyright:
© 2014 the American Physiological Society.

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