TY - JOUR
T1 - Targeting GPCR Signaling for Idiopathic Pulmonary Fibrosis Therapies
AU - Haak, Andrew J.
AU - Ducharme, Merrick T.
AU - Diaz Espinosa, Ana M.
AU - Tschumperlin, Daniel J.
N1 - Funding Information:
We thank the past and present members of the laboratory of D.J.T. and our collaborators and colleagues who have contributed to our understanding of GPCR pathways and downstream effectors in fibrosis. We acknowledge funding from the National Institutes of Health (NIH; HL133320 and HL092961 ) and the US Department of Defense ( PR181132 ), a Boehringer Ingelheim Discovery Award in Interstitial Lung Disease, a American Lung Association Catalyst Award, and a Pulmonary Fibrosis Foundation Scholars Award.
Funding Information:
We thank the past and present members of the laboratory of D.J.T. and our collaborators and colleagues who have contributed to our understanding of GPCR pathways and downstream effectors in fibrosis. We acknowledge funding from the National Institutes of Health (NIH; HL133320 and HL092961) and the US Department of Defense (PR181132), a Boehringer Ingelheim Discovery Award in Interstitial Lung Disease, a American Lung Association Catalyst Award, and a Pulmonary Fibrosis Foundation Scholars Award.
Publisher Copyright:
© 2020 Elsevier Ltd
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/3
Y1 - 2020/3
N2 - 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.
AB - 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.
KW - G protein-coupled receptor
KW - MRTF
KW - ROCK
KW - TAZ
KW - YAP
KW - fibrosis
UR - http://www.scopus.com/inward/record.url?scp=85078794633&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85078794633&partnerID=8YFLogxK
U2 - 10.1016/j.tips.2019.12.008
DO - 10.1016/j.tips.2019.12.008
M3 - Review article
C2 - 32008852
AN - SCOPUS:85078794633
VL - 41
SP - 172
EP - 182
JO - Trends in Pharmacological Sciences
JF - Trends in Pharmacological Sciences
SN - 0165-6147
IS - 3
ER -