Targeting GPCR Signaling for Idiopathic Pulmonary Fibrosis Therapies

Trends Pharmacol Sci. 2020 Mar;41(3):172-182. doi: 10.1016/j.tips.2019.12.008. Epub 2020 Jan 30.

Abstract

A variety of G protein-coupled receptors (GPCRs) have been implicated in the pathogenesis of pulmonary fibrosis, largely through their promotion of profibrotic fibroblast activation. By contrast, recent work has highlighted the beneficial effects of Gαs-coupled GPCRs on reducing fibroblast activation and fibrosis. This review highlights how fibrosis-promoting and -inhibiting GPCR signaling converges on downstream signaling and transcriptional effectors, and how the diversity and dynamics of GPCR expression challenge efforts to identify effective therapies for idiopathic pulmonary fibrosis (IPF). Next-generation strategies to overcome these challenges, focusing on target selection, polypharmacology, and personalized medicine approaches, are discussed as a path towards more effective GPCR-targeted therapies for pulmonary fibrosis.

Keywords: G protein-coupled receptor; MRTF; ROCK; TAZ; YAP; fibrosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Fibrosis
  • Humans
  • Idiopathic Pulmonary Fibrosis* / drug therapy
  • Polypharmacology
  • Receptors, G-Protein-Coupled
  • Signal Transduction

Substances

  • Receptors, G-Protein-Coupled