Glucocorticoids Retain Bipotent Fibroblast Progenitors during Alveolar Septation in Mice

American Journal of Respiratory Cell and Molecular Biology
Stephen E McGowan, Diann M McCoy

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 ...Continue Reading

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Citations

Mar 16, 2018·American Journal of Physiology. Lung Cellular and Molecular Physiology·Stephen E McGowan, Diann M McCoy
Mar 7, 2019·American Journal of Physiology. Lung Cellular and Molecular Physiology·Stephen E McGowan
Oct 10, 2019·American Journal of Physiology. Lung Cellular and Molecular Physiology·Ettore LignelliRory E Morty

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