Nrf2 activation attenuates diabetic kidney disease in preclinical in vitro and in vivo mouse model

초록

Background and aims: Diabetic kidney disease (DKD) is one of the most common cause of chronic kidney disease, and its incidence is expected to rise with mounting incidence of diabetes mellitus in Korea. Literatures show that nuclear 1 factor (erythroid-derived 2)-related factor 2 (Nrf2) has low activity in diabetic kidney, and its activation has antioxidant and anti-infammatory efects that can be utilized in treating multiple kidney diseases. This study investigated the efect of Nrf2 in murine mesangial cell culture and DKD mouse model, by the use of a pharmacological Nrf2 agonist. Materials and methods: 10-week-old mice were given streptozotocin to induce DKD, and were divided into groups to be given either control or a Nrf2 activator compound by oral gavage for 7 weeks. 9-week-old db/db mice and control db/m mice were also given either control or a Nrf2 activator by oral gavage for 12 weeks. SV40-MES13 mouse mesangial cell line was purchased and treated for 48hr with high glucose media and a Nrf2 activator. Results: In DKD mice model, pharmacological Nrf2 activation reduced albuminuria, restored DKD-induced glomerular damage and mesangial thickening, and increased expression of anti-infammatory genes. Mesangial cell culture showed that Nrf2 activator suppressed mesangial cell proliferation. Conclusion: Inducing Nrf2 activation could be a promising therapeutic target for alleviating DKD.