Podocyte-specific knockout of cyclooxygenase 2 exacerbates diabetic kidney disease.

Published

Journal Article

Enhanced expression of cyclooxygenase 2 (COX2) in podocytes contributes to glomerular injury in diabetic kidney disease, but some basal level of podocyte COX2 expression might be required to promote podocyte attachment and/or survival. To investigate the role of podocyte COX2 expression in diabetic kidney disease, we deleted COX2 specifically in podocytes in a mouse model of Type 1 diabetes mellitus (Akita mice). Podocyte-specific knockout (KO) of COX2 did not affect renal morphology or albuminuria in nondiabetic mice. Albuminuria was significantly increased in wild-type (WT) and KO Akita mice compared with nondiabetic controls, and the increase in albuminuria was significantly greater in KO Akita mice compared with WT Akita mice at both 16 and 20 wk of age. At the 20-wk time point, mesangial expansion was also increased in WT and KO Akita mice compared with nondiabetic animals, and these histologic abnormalities were not improved by KO of COX2. Tubular injury was seen only in diabetic mice, but there were no significant differences between groups. Thus, KO of COX2 enhanced albuminuria and did not improve the histopathologic features of diabetic kidney disease. These data suggest that 1) KO of COX2 in podocytes does not ameliorate diabetic kidney disease in Akita mice, and 2) some basal level of podocyte COX2 expression in podocytes is necessary to attenuate the adverse effects of diabetes on glomerular filtration barrier function.

Full Text

Duke Authors

Cited Authors

  • Wang, L; Sha, Y; Bai, J; Eisner, W; Sparks, MA; Buckley, AF; Spurney, RF

Published Date

  • August 1, 2017

Published In

Volume / Issue

  • 313 / 2

Start / End Page

  • F430 - F439

PubMed ID

  • 28490532

Pubmed Central ID

  • 28490532

Electronic International Standard Serial Number (EISSN)

  • 1522-1466

Digital Object Identifier (DOI)

  • 10.1152/ajprenal.00614.2016

Language

  • eng

Conference Location

  • United States