A maladaptive role for EP4 receptors in podocytes

LAUR Repository

Show simple item record

dc.contributor.author Faour, Wissam
dc.contributor.author Stitt-Cavanagh, Erin
dc.contributor.author Takami, Kaede
dc.contributor.author Carter, Anthony
dc.contributor.author Vaderhyden, Barbara
dc.contributor.author Ghan, Youfei
dc.contributor.author Schendeir, Andre
dc.contributor.author Breyer, Mathieu
dc.contributor.author Kennedy, Christopher
dc.date.accessioned 2015-10-23T08:16:58Z
dc.date.available 2015-10-23T08:16:58Z
dc.date.copyright 2010
dc.date.issued 2015-10-23
dc.identifier.citation Stitt-Cavanagh, E. M., Faour, W. H., Takami, K., Carter, A., Vanderhyden, B., Guan, Y., ... & Kennedy, C. R. (2010). A maladaptive role for EP4 receptors in podocytes. Journal of the American Society of Nephrology, 21(10), 1678-1690. en_US
dc.description.abstract Inhibition of p38 mitogen-activated protein kinase and cyclooxygenase-2 reduces albuminuria in models of chronic kidney disease marked by podocyte injury. Previously, we identified a feedback loop in podocytes whereby an in vitro surrogate for glomerular capillary pressure (i.e., mechanical stretch) along with prostaglandin E2 stimulation of its EP4 receptor induced cyclooxygenase-2 in a p38-dependent manner. Here we asked whether stimulation of EP4 receptors would exacerbate glomerulopathies associated with enhanced glomerular capillary pressure. We generated mice with either podocyte-specific overexpression or depletion of the EP4 receptor (EP4pod+ and EP4pod−/−, respectively). Glomerular prostaglandin E2-stimulated cAMP levels were eightfold greater for EP4pod+ mice compared with nontransgenic (non-TG) mice. In contrast, EP4 mRNA levels were >50% lower, and prostaglandin E2-induced cAMP synthesis was absent in podocytes isolated from EP4pod−/− mice. Non-TG and EP4pod+ mice underwent 5/6 nephrectomy and exhibited similar increases in systolic BP (+25 mmHg) by 4 weeks compared with sham-operated controls. Two weeks after nephrectomy, the albumin-creatinine ratio of EP4pod+ mice (3438 μg/mg) was significantly higher than that of non-TG mice (773 μg/mg; P < 0.0001). Consistent with more severe renal injury, the survival rate for nephrectomized EP4pod+ mice was significantly lower than that for non-TG mice (14 versus 67%). In contrast, 6 weeks after nephrectomy, the albumin-creatinine ratio of EP4pod−/− mice (753 μg/mg) was significantly lower than that of non-TG mice (2516 μg/mg; P < 0.05). These findings suggest that prostaglandin E2, acting via EP4 receptors contributes to podocyte injury and compromises the glomerular filtration barrier. en_US
dc.title A maladaptive role for EP4 receptors in podocytes
dc.author.school SOM en_US
dc.author.idnumber 200904962 en_US
dc.author.woa N/A en_US
dc.author.department N/A en_US
dc.description.embargo N/A en_US
dc.relation.journal Journal of the American Society of Nephrology en_US
dc.journal.volume 21 en_US
dc.journal.issue 10 en_US
dc.article.pages 1678-1690 en_US
dc.author.email wissam.faour@lau.edu.lb
dc.identifier.url http://jasn.asnjournals.org/content/21/10/1678.short

Files in this item

This item appears in the following Collection(s)

Show simple item record

Search LAUR

Advanced Search


My Account