BRD4 contributes to high-glucose-induced podocyte injury by modulating Keap1/Nrf2/ARE signaling.

In this study, we aimed to explore the potential role of BRD4 in regulating HG-induced podocyte injury and its underlying molecular mechanism. HG exposure significantly upregulated BRD4 in podocytes. BRD4 inhibition by small interfering RNA or its chemical inhibitor (JQ1) markedly repressed HG-induced apoptosis and reactive oxygen species (ROS) production. By contrast, BRD4 overexpression exacerbated HG-induced podocyte injury. Moreover, BRD4 inhibition potentiated nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling associated with suppression of Kelch-like ECH-associated protein (Keap1). BRD4 inhibition promoted Nrf2 nuclear translocation and upregulated the transcriptional activity of Nrf2/antioxidant response element (ARE). However, Nrf2 silencing partially reversed BRD4-inhibition-mediated protection against HG-induced podocyte injury. Overall, these results suggest that BRD4 inhibition confers cytoprotection against HG injury in podocytes through potentiation of Nrf2/ARE antioxidant signaling. This finding implicates BRD4/Nrf2/ARE signaling in the pathogenesis of diabetic nephropathy. PMID: 31325480 [PubMed - as supplied by publisher]
Source: Biochimie - Category: Biochemistry Authors: Tags: Biochimie Source Type: research