Ｏｂｊｅｃｔｉｖｅ：Podocyte injury results in disruption of the glomerular filtration integrity and proteinuria,which is commonly seen in various types of glomerular diseases.Nuclear factor erythroid2related factor 2 (Nrf2) plays a central role in the defense against oxidative stress.We investigated whether Nrf2 activation protected against puromycin aminonucleotide (PAN) induced podocyte injury in vitro.
Ｍｅｔｈｏｄｏｌｏｇｙ：PAN treated podocytes for 24 h in vitro to establish a podocyte injury model.Bardoxolone methyl (CDDOMe),an activator of the Nrf2 pathway,acts as a therapeutic agent in this experiment.The podocytes were randomly divided into normal group,PAN group (PAN 100 μg/ml),CDDOME control group (CDDOMe 100 μmol/L),CDDOME protection group (PAN 100 μg/ml+CDDOME 100 μmol/L).Nrf2 protein levels were detected by Westernblot.qRTPCR was used to detect the mRNA expression of IL1,TNFa,Nrf2,geneoxidoreductase1 (NQO1),heme oxygenase (HO1).Apoptosis was detected with annexin V/PI staining by flow cytometry.
Ｒｅｓｕｌｔｓ：CDDOME treatment led to Nrf2 nuclear translocation and increased Nrf2 mRNA and protein level in podocytes,which enhanced the Nrf2 downstream NQO1 and HO1 expression in a Nrf2 dependent manner.In PANinduced podocyte injury,CDDOME exhibited cytoprotective effects by enhancing the Nrf2ARE regulated antioxidant system and diminished the PANinduced inflammatory response as well as apoptosis via a Nrf2 dependent pathway.
Ｃｏｎｃｌｕｓｉｏｎ：Nrf2 activation protected podocyte from injury through balancing oxidative stress and suppressing inflammatory responses.