NRF2‐suppressed vascular calcification by regulating the antioxidant pathway in chronic kidney disease

• DOI: 10.1096/fj.202100625rr
• Publication Date: 2021-12-17T08:45:23Z
• Authors: Donghua Jin; Lihua Lin; Yuxian Xie; Miao Jia; Hong Qiu; Kang Xun
• Keywords: Osteopontin; RUNX2; Malondialdehyde

Vascular calcification (VC), in which vascular smooth muscle cells (VSMCs) undergo differentiation and osteogenic transition, is a common complication of chronic kidney disease (CKD). Recent findings show that nuclear factor-erythroid-2-related factor 2 (NRF2) an evolutionarily conserved antioxidant beneficial preventing senescence calcification. The roles NRF2 the initiation progression VC CKD still need further investigation. CKD-associated model rats exhibited significant upregulation NRF2, NAD(P)H: quinone oxidoreductase-1 (NQO1), markers such as alkaline phosphatase (ALP), runt-related transcription factor-2 (RUNX2) osteopontin (OPN), β-catenin compared to rats. Immunohistochemistry verified these results. In addition, rat aortic VSMCs were isolated subjected four treatments: normal control, phosphorus-induced (Pi), Pi + activator DMF, inhibitor ML385. reactive oxygen species (ROS) generation, malondialdehyde (MDA) content, calcium deposition treatments determined. mRNA protein expression levels NQO1, haem oxygenase 1 (HO1) ALP, Runx1, OPN, bone morphogenetic (BMP2), quantified by RT-PCR western blotting. VSMC apoptosis was calculated flow cytometry. vitro results suggested intracellular oxidative stress closely associated with activity activation could significantly suppress transition VSMCs. Thus, this study indicated NRF2-related pathway can positively respond protect against reducing stress. This may contribute insights facilitating application antioxidative system therapeutic treatment for diseases CKD.