Activation of Akt‐dependent Nrf2/ARE pathway by restoration of Brg‐1 remits high glucose‐induced oxidative stress and ECM accumulation in podocytes

Abstract Brahma‐related gene 1 (Brg‐1) is perceived as a cytoprotective protein due to its role in alleviating oxidative stress and apoptosis. Our study aimed to explore the role and mechanism of Brg‐1 in high glucose (HG)‐stimulated podocytes. The HG exposure downregulated Brg‐1 and inactivated the protein kinase B (Akt) pathway in podocytes. Restoration of Brg‐1 inhibited HG‐induced viability reduction of podocytes. The HG‐induced increase of reactive oxygen species and malondialdehyde levels and decrease of superoxide dismutase activity in podocytes were reversed by the Brg‐1 overexpression. The Brg‐1 overexpression terminated the HG‐induced production of fibronectin, collagen IV, transforming growth factor‐β1, and connective tissue growth factor. In addition, the Brg‐1 overexpression activated Akt‐dependent nuclear factor E2‐related factor 2 (Nrf2)/antioxidant response element (ARE) signaling in HG‐stimulated podocytes. However, inhibition of the Akt pathway or Nrf2 silencing counteracted the protective effects of Brg‐1 in HG‐stimulated podocytes. In conclusion, the Brg‐1 overexpression suppressed HG‐induced oxidative stress and extracellular matrix accumulation by activation of Akt‐dependent Nrf2/ARE signaling in podocytes.