Department of Nephrology, Nanyang First People's Hospital, Nanyang, China.
Department of ICU, Lianshui County People's Hospital Affiliated to Kangda College of Nanjing Medical University, Huai'an, China.
J Biochem Mol Toxicol. 2021 Mar;35(3):e22672. doi: 10.1002/jbt.22672. Epub 2020 Dec 3.
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.
Brahma 相关基因 1（Brg-1）被认为是一种细胞保护蛋白，因为它在缓解氧化应激和细胞凋亡方面发挥作用。我们的研究旨在探讨 Brg-1 在高葡萄糖（HG）刺激的足细胞中的作用和机制。HG 暴露下调了足细胞中的 Brg-1 并使蛋白激酶 B（Akt）途径失活。Brg-1 的恢复抑制了 HG 诱导的足细胞活力降低。Brg-1 的过表达逆转了 HG 诱导的足细胞中活性氧和丙二醛水平的增加以及超氧化物歧化酶活性的降低。Brg-1 的过表达终止了 HG 诱导的纤维连接蛋白、IV 型胶原、转化生长因子-β1 和结缔组织生长因子的产生。此外，Brg-1 的过表达激活了 Akt 依赖性核因子 E2 相关因子 2（Nrf2）/抗氧化反应元件（ARE）信号通路在 HG 刺激的足细胞中。然而，Akt 通路的抑制或 Nrf2 的沉默抵消了 Brg-1 在 HG 刺激的足细胞中的保护作用。总之，Brg-1 的过表达通过激活 Akt 依赖性 Nrf2/ARE 信号通路抑制了 HG 诱导的氧化应激和细胞外基质积聚。
