Glucocorticoid Regulates Mesenchymal Cell Differentiation Required for Perinatal Lung Morphogenesis and Function.

Glucocorticoid Regulates Mesenchymal Cell Differentiation Required for Perinatal Lung Morphogenesis and Function. Am J Physiol Lung Cell Mol Physiol. 2020 May 27;: Authors: Bridges JP, Sudha P, Lipps D, Wagner A, Guo M, Du Y, Brown K, Filuta A, Kitzmiller JA, Stockman C, Chen X, Weirauch MT, Jobe AH, Whitsett JA, Xu Y Abstract While antenatal glucocorticoids are widely used to enhance lung function in preterm infants, cellular and molecular mechanisms by which glucocorticoid receptor (GR) signaling influences lung maturation remain poorly understood. Deletion of the glucocorticoid receptor gene (Nr3c1) from fetal pulmonary mesenchymal cells phenocopied defects caused by global Nr3c1 deletion, while lung epithelial- or endothelial-specific Nr3c1 deletion did not impair lung function at birth. We integrated genome-wide gene expression profiling, ATAC-seq, and single cell RNA-seq data in mice in which GR was deleted or activated to identify the cellular and molecular mechanisms by which glucocorticoids control prenatal lung maturation. GR enhanced differentiation of a newly defined proliferative mesenchymal progenitor cell (PMP) into matrix fibroblasts (MFB), in part by directly activating extracellular matrix-associated target genes, including Fn1, Col16a4, and Eln and by modulating VEGF, JAK-STAT and WNT signaling. Loss of mesenchymal GR signaling blocked fibroblast progenitor differentiation into mature MFB, which in turn increased p...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - Category: Cytology Authors: Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research