Glucocorticoids Retain Bipotent Fibroblast Progenitors during Alveolar Septation in Mice

Stephen E McGowan; Diann M McCoy

doi:10.1165/rcmb.2016-0376OC

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Glucocorticoids Retain Bipotent Fibroblast Progenitors during Alveolar Septation in Mice

Journal article

Open access

Peer reviewed

Glucocorticoids Retain Bipotent Fibroblast Progenitors during Alveolar Septation in Mice

Stephen E McGowan and Diann M McCoy

American journal of respiratory cell and molecular biology, Vol.57(1), pp.111-120

07/2017

DOI: 10.1165/rcmb.2016-0376OC

PMCID: PMC5946667

PMID: 28530121

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https://europepmc.org/articles/pmc5946667View

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Abstract

Glucocorticoids have been widely used and exert pleiotropic effects on alveolar structure and function, but do not improve the long-term clinical outcomes for patients with bronchopulmonary dysplasia, emphysema, or interstitial lung diseases. Treatments that foster alveolar regeneration could substantially improve the long-term outcomes for such patients. One approach to alveolar regeneration is to stimulate and guide intrinsic alveolar progenitors along developmental pathways used during secondary septation. Other investigators and we have identified platelet-derived growth factor receptor-α-expressing fibroblast subpopulations that are alternatively skewed toward myofibroblast or lipofibroblast phenotypes. In this study, we administered either the glucocorticoid receptor agonist dexamethasone (Dex) or the antagonist mifepristone to mice during the first postnatal week and evaluated their effects on cellular proliferation and adoption of α-smooth muscle actin and lipid droplets (markers of the myofibroblast and lipofibroblast phenotypes, respectively). We observed that Dex increased the relative abundance of fibroblasts with progenitor characteristics, i.e., containing both α-smooth muscle actin and lipid droplets, uncoupling protein-1 (a marker of brown and beige adipocytes), delta-like ligand-1, and stem cell antigen-1. Dex enhanced signaling through the Smad1/5 pathway, which increased uncoupling protein-1 in a lung fibroblast progenitor cell line. We conclude that glucocorticoid receptor manipulation can sustain fibroblast plasticity, and posit that targeting downstream glucocorticoid responsive pathways could steer fibroblast progenitors along more desirable regenerative pathways.

Signal Transduction

Adipocytes, Brown - cytology

Adipocytes, Brown - metabolism

Animals

Cell Proliferation - drug effects

Dexamethasone - pharmacology

Fibroblasts - cytology

Fibroblasts - drug effects

Fibroblasts - metabolism

Glucocorticoids - pharmacology

Green Fluorescent Proteins - metabolism

Lipid Droplets - drug effects

Lipid Droplets - metabolism

Lipid Metabolism - drug effects

Mice

Mifepristone - pharmacology

Phosphorylation - drug effects

Pulmonary Alveoli - drug effects

Pulmonary Alveoli - growth & development

Pulmonary Alveoli - metabolism

Receptor, Platelet-Derived Growth Factor alpha - metabolism

Smad Proteins - metabolism

Stem Cells - cytology

Stem Cells - drug effects

Stem Cells - metabolism

Uncoupling Protein 1 - metabolism

Details

Title: Subtitle: Glucocorticoids Retain Bipotent Fibroblast Progenitors during Alveolar Septation in Mice
Creators: Stephen E McGowan
Diann M McCoy - University of Iowa
Resource Type: Journal article
Publication Details: American journal of respiratory cell and molecular biology, Vol.57(1), pp.111-120
DOI: 10.1165/rcmb.2016-0376OC
PMID: 28530121
PMCID: PMC5946667
ISSN: 1044-1549
eISSN: 1535-4989
Grant note: S10 RR027219 / NCRR NIH HHS I01 BX000508 / BLRD VA
Language: English
Date published: 07/2017
Academic Unit: Pulmonary, Critical Care, and Occupational Medicine; International Programs; Internal Medicine
Record Identifier: 9984359574402771

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5 Times Cited - Web of Science

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