Figure 1: Proposed mechanism of Nrf2 activation on Agt gene expression in RPTs: Under normal conditions, Nrf2 is bound to Keap1 in the cytoplasm and is subject to ubiquitination and proteasome degradation. Upon exposure to high glucose (HG), oxidative stressor or Nrf2 activators (oltipraz), Nrf2-Keap1 complexes dissociate and Nrf2 translocates to the nucleus. Nrf2 binds to Nrf2-REs in the Agt gene promoter, stimulating Agt gene transcription and intrarenal RAS activation, and leading to the development of hypertension and nephropathy in diabetes. TSS (transcriptional start site)