The aryl hydrocarbon receptor: An environmental effector in the pathogenesis of fibrosis. (October 2020)

• Record Type: Journal Article
• Authors: Shi, Yaqian; Zeng, Zhuotong; Yu, Jiangfan; Tang, Bingsi; Tang, Rui; Xiao, Rong
• Is Part Of: Pharmacological research. Volume 160(2020)
• Publication Date: 2020-10
• Subjects: AhR aryl hydrocarbon receptor -- CYP cytochrome P450 -- CYP1A1, B1 cytochrome P450 family A1, B1 -- ECM extracellular matrix -- MMPs matrix metalloproteinases -- TGF-β transforming growth factor-beta -- ARNT AhR nuclear translocator -- XRE xenobiotic-responsive element -- AhRE aryl hydrocarbon-responsive element -- I3C indole 3-carboline -- ICZ indole[3, 2-b] carb azole -- DIM 3, 3-diindolylmethane -- Trp tryptophan -- Kyn kynurenine -- ITE 2-(1′H-indole-3-carbonyl)-4-carboxylic acid methyl thiazole -- FICZ 6-formyl indole-(3, 2-b)-carbazole -- α-SMA α-smooth muscle actin -- EMT epithelial-to-mesenchymal transition -- MMT mesothelial-to-mesenchymal transition -- EndoMT endothelial-to-mesenchymal transition -- TNF-α, TNF-γ tumor necrosis factor-α -- IL-1β, IL-6 interleukin-1β, -6 -- LTBP latent TGF-β binding protein -- TED thyroid eye disease -- PPIs proton pump inhibitors -- HSCs hepatic stellate cells; Aryl hydrocarbon receptor -- Fibrosis -- Myofibroblast -- TGF-β -- Matrix metalloproteinases; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2020.105180
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Highlights: The aryl hydrocarbon receptor (AhR) is a highly conserved transcription factor that can be activated by abundant ligands. AhR signaling can regulate TGF-β activity, myofibroblast activation, ECM degradation. The screening of new AhR ligands (SAhRMs and RMAhRLs) may be candidate compounds for future fibrosis prevention and treatment. Abstract: The aryl hydrocarbon receptor (AhR) is a highly conserved transcription factor that can be activated by small molecules provided by dietary, plant, or microbial metabolites, and environmental pollutants. AhR is expressed in many cell types and engages in crosstalk with other signaling pathways, and therefore provides a molecular pathway that integrates environmental cues and metabolic processes. Fibrosis, which is defined as an aberrant extracellular matrix formation, is a reparative process in the terminal stage of chronic diseases. Both environmental and internal factors have been shown to participate in the pathogenesis of fibrosis; however, the underlying mechanisms still remain elusive. In this review, the potential role of AhR in the process of fibrosis, as well as potential opportunities and challenges in the development of AhR targeting therapeutics, are summarized.