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Publication
Podocyte-specific soluble epoxide hydrolase deficiency in mice attenuates acute
kidney injury.
Authors Bettaieb A, Koike S, Chahed S, Zhao Y, Bachaalany S, Hashoush N, Graham J,
Fatima H, Havel PJ, Gruzdev A, Zeldin DC, Hammock BD, Haj FG
Submitted By Submitted Externally on 7/27/2017
Status Published
Journal The FEBS journal
Year 2017
Date Published 7/1/2017
Volume : Pages 284 : 1970 - 1986
PubMed Reference 28485854
Abstract Podocytes play an important role in maintaining glomerular function, and
podocyte injury is a significant component in the pathogenesis of proteinuria.
Soluble epoxide hydrolase (sEH) is a cytosolic enzyme whose genetic deficiency
and pharmacological inhibition have beneficial effects on renal function, but
its role in podocytes remains unexplored. The objective of this study was to
investigate the contribution of sEH in podocytes to lipopolysaccharide
(LPS)-induced kidney injury. We report increased sEH transcript and protein
expression in murine podocytes upon LPS challenge. To determine the function of
sEH in podocytes in vivo we generated podocyte-specific sEH-deficient
(pod-sEHKO) mice. Following LPS challenge, podocyte sEH-deficient mice exhibited
lower kidney injury, proteinuria, and blood urea nitrogen concentrations than
controls suggestive of preserved renal function. Also, renal mRNA and serum
concentrations of inflammatory cytokines IL-6, IL-1ß, and TNFa were
significantly lower in LPS-treated pod-sEHKO than control mice. Moreover,
podocyte sEH deficiency was associated with decreased LPS-induced NF-?B and MAPK
activation and attenuated endoplasmic reticulum stress. Furthermore, the
protective effects of podocyte sEH deficiency in vivo were recapitulated in E11
murine podocytes treated with a selective sEH pharmacological inhibitor.
Altogether, these findings identify sEH in podocytes as a contributor to
signaling events in acute renal injury and suggest that sEH inhibition may be of
therapeutic value in proteinuria., Soluble epoxide hydrolase: EC 3.3.2.10.




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