Nox4 and kidney function – Vascular Research Centre

Nox 4 and kidney function

The NADPH oxidase 4, differently from the other 6 Nox enzymes, produces H2O2 and is constitutively active. It was described in 1999 and named Renox due to its high expression in the kidney. Years later it became a pharmacological target in kidney fibrosis and Nox4 inhibitors emerged as a potential therapy. However, inhibitors showed no beneficial effect and failed at clinical phase II. In this project, we study the physiological function of Nox4 in the kidney which is so far totally unknown. In fact, in renal diabetic disease Nox4 expression is reduced suggesting its important role in maintaining normal function of the healthy kidney. With the aid of Nox4 knockout (inducible, global and tissue specific) and knock-in mice we perform all experiments in vivo and employ untargeted metabolomics, bioinformatics for metabolic reconstruction (FASTACORMICS and Recon 3), targeted LC/MS, renal clearance and state of art biochemical techniques to uncover the physiological function of Nox4 in the kidney.