Fig. 2.

Potential consequences of Nrf2-mediated ECM alterations. Activation of Nrf2 in fibroblasts results in numerous changes in the production and deposition of ECM. The modified ECM typically features reduced collagen and increased levels of certain glycoproteins and other ECM-affiliated proteins such as PAI-1. Nrf2-mediated regulation of ECM can take place by directly targeting specific ECM genes, or indirectly by modulating ROS levels and ROS-dependent signaling pathways (e.g. TGF-b signaling) which can influence myofibroblast differentiation and ECM synthesis. This Nrf2-ECM can impact interacting cells and associated tissues, which may result in the development of a CAF phenotype and/or fibroblast senescence via PAI-1. Together, this may accelerate epithelial cell proliferation, aiding tissue repair and reducing scarring, but may also contribute to increased tumor growth. Abbreviations: PAI-1 (plasminogen activator inhibitor-1): Gcp1 (glypican-1); Angptl2 (angiopoietin-like protein 2).