Journal article
Genetic targeting or pharmacologic inhibition of NADPH oxidase Nox4 provides renoprotection in long-term diabetic nephropathy
JC Jha, SP Gray, D Barit, J Okabe, A El-Osta, T Namikoshi, V Thallas-Bonke, K Wingler, C Szyndralewiez, F Heitz, RM Touyz, ME Cooper, HHHW Schmidt, KA Jandeleit-Dahm
Journal of the American Society of Nephrology | AMER SOC NEPHROLOGY | Published : 2014
Abstract
Diabetic nephropathymay occur, in part, as a result of intrarenal oxidative stress. NADPH oxidases comprise the only known dedicated reactive oxygen species (ROS)-forming enzyme family. In the rodent kidney, three isoforms of the catalytic subunit of NADPH oxidase are expressed (Nox1, Nox2, and Nox4). Here we show that Nox4 is the main source of renal ROS in a mouse model of diabetic nephropathy induced by streptozotocin administration in ApoE-/- mice. Deletion of Nox4, but not of Nox1, resulted in renal protection from glomerular injury as evidenced by attenuated albuminuria, preserved structure, reduced glomerular accumulation of extracellular matrix proteins, attenuated glomerular macroph..
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Awarded by European Commission
Funding Acknowledgements
This work was supported by grants from the National Health & Medical Research Council (NHMRC) of Australia, the Juvenile Diabetes Research Foundation (JDRF), the Diabetes Australia Research Trust, and the FP7 Framework Programme. K.A.J.-D. is supported by a NHMRC Senior Research Fellowship. M.E.C. is an Australian Fellow for the NHMRC and a recipient of a JDRF Scholars Award. H.H.H.W.S. is supported by a Marie Curie International reintegration grant, a European Research Council advanced investigator grant, and the Dutch Kidney Foundation. R.M.T. was supported by a Canada Research Chair/Canadian Institutes of Health Research/Canadian Foundation for Innovation award.