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Deletion of soluble epoxide hydrolase gene improves renal endothelial function and reduces renal inflammation and injury in streptozotocin‐induced type 1 diabetes
Author(s) -
Elmarakby Ahmed A.,
Faulkner Jessica,
AlShabrawey Mohammed,
Wang MongHeng,
Imig John
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.664.10
Subject(s) - epoxide hydrolase 2 , endocrinology , medicine , streptozotocin , diabetes mellitus , renal function , diabetic nephropathy , kidney , chemistry , biochemistry , enzyme
Inhibition of soluble epoxide hydrolase (sEH) provides renal protection in salt‐sensitive hypertension. We hypothesize that targeted disruption of the sEH gene (Ephx2) improves endothelial function and reduces renal damage in streptozotocin‐induced diabetic renal injury. Afferent arteriolar relaxation to acetylcholine was impaired in WT diabetic mice compared to WT control and Ephx2 gene KO improved relaxation in diabetes. Urinary MCP‐1 excretion greatly increased in WT diabetic compared to WT control (868±195 vs. 31.5±7 pg/day) and this was attenuated in Ephx2 KO diabetic mice (420±98 pg/day). The renal phospho‐IKK/IKK ratio and NFKappaB as well as NADPH oxidase activity and TBARs excretion all significantly decreased while hemeoxygenase‐1 (HO‐1) expression increased in Ephx2 KO diabetic compared to WT diabetic mice. Albuminuria was also elevated in WT diabetic mice compared to WT control (170±43 vs. 37±13 (g/day) and Ephx2 KO reduced this elevation in diabetes (50±15 (g/day). We postulate that inhibition of NFkappaB signaling and activation of the HO‐1 antioxidant mechanism contributes to decreased renal injury in Ephx2 KO diabetic mice.