The Nrf2 transcription factor: A multifaceted regulator of the extracellular matrix

Abstract

The transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) is widely recognized as a master regulator of the cellular stress response by facilitating the transcription of cytoprotective genes. As such, the Nrf2 pathway is critical in guarding the cell from the harmful effects of excessive reactive oxygen species/reactive nitrogen species (ROS/RNS) and in maintaining cellular redox balance. While excessive ROS/RNS are harmful to the cell, physiological levels of ROS/RNS play important roles in regulating numerous signaling pathways important for normal cellular function, including the synthesis of extracellular matrix (ECM). Recent advances have underscored the importance of ROS/RNS, and by extension, factors that influence redox-balance such as Nrf2, in regulating ECM production and deposition. In addition to reducing the oxidative burden in the cell, the discovery that Nrf2 can also directly target genes that regulate and form the ECM has cemented it as a multifaceted player in the regulation of ECM proteins, and provides new insight into its potential usefulness as a target for treating ECM-related pathologies.