BioAcyl Corp
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Hiebert, P. (2021). The Nrf2 transcription factor: A multifaceted regulator of the extracellular matrix. Matrix Biology Plus, 10, 100057. Added by: Dr. Enrique Feoli (22/09/2025, 22:18) Last edited by: Dr. Enrique Feoli (22/09/2025, 23:29) |
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| Resource type: Journal Article DOI: 10.1016/j.mbplus.2021.100057 ID no. (ISBN etc.): 2590-0285 BibTeX citation key: Hiebert2021 View all bibliographic details  |
Categories: BioAcyl Corp, BioAcyl Corp Subcategories: Disease Tolerance, Homeostasis Keywords: Extracellular Matrix, Matrisome, Nuclear factor-erythroid 2-related factor 2 (Nrf2), Reactive oxygen species/reactive nitrogen species (ROS/RNS), Senescence, tissue repair Creators: Hiebert Collection: Matrix Biology Plus |
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| Abstract |
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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.
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Actions of ROS/RNS on the ECM. ROS/RNS regulate the ECM in several ways. Degradation of glycosaminoglycans (GAGs) can be achieved by reacting directly with ROS/RNS or by the actions of ROS/RNS-regulated enzymes. ROS/RNS react with MMPs, thereby promoting their activation. Myofibroblast differentiation is regulated by ROS/RNS to facilitate intracellular TGF-β signaling, and can promote the release of sequestered TGF-β from the ECM (e.g. by reacting with LAP). Several transcription factors, including Nrf2, are regulated via the actions of ROS/RNS, and can promote the transcription of ECM genes. ROS/RNS also react with certain residues on ECM molecules to promote cross-linking. Added by: Dr. Enrique Feoli Last edited by: Dr. Enrique Feoli |