The aryl hydrocarbon receptor: An environmental effector in the pathogenesis of fibrosis

Pharmacol Res. 2020 Oct:160:105180. doi: 10.1016/j.phrs.2020.105180. Epub 2020 Aug 30.

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.

Keywords: Aryl hydrocarbon receptor; Fibrosis; Matrix metalloproteinases; Myofibroblast; TGF-β.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Environmental Pollutants / toxicity*
  • Fibrosis / chemically induced*
  • Fibrosis / pathology
  • Humans
  • Receptors, Aryl Hydrocarbon / drug effects*

Substances

  • AHR protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • Environmental Pollutants
  • Receptors, Aryl Hydrocarbon