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Targeting GPCR Signaling for Idiopathic Pulmonary Fibrosis Therapies.

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 G?s-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.

SUBMITTER: Haak AJ

PROVIDER: S-EPMC7856568 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Targeting GPCR Signaling for Idiopathic Pulmonary Fibrosis Therapies.

Haak Andrew J AJ Ducharme Merrick T MT Diaz Espinosa Ana M AM Tschumperlin Daniel J DJ

Trends in pharmacological sciences 20200130 3

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 ...[more]

PMID: 32008852

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