title: Platelet-derived growth factor receptor-alpha-expressing cells localize to the alveolar entry ring and have characteristics of myofibroblasts during pulmonary alveolar septal formation.
abstract: Platelet-derived growth factor-A and its receptor, platelet-derived growth factor receptor-alpha (PDGF-Ralpha), are required for formation of the secondary pulmonary alveolar septa in mice. However, it remains unclear how these molecules direct the secondary septation process. We have examined the abundance, location, and the accumulation of alpha-smooth muscle actin (alphaSMA), neutral lipid droplets, and elastin in the proximity of PDGF-Ralpha-expressing alveolar cells during postnatal days 4 through 12 in the mouse. PDGF-Ralpha-expressing cells preferentially have characteristics of myofibroblasts and were more likely to contain alphaSMA than are alveolar cells that do not express PDGF-Ralpha. PDGF-Ralpha expressing cells were preferentially located in the alveolar entry ring (AER) where alphaSMA and elastic fibers accumulate. In contrast, PDGF-Ralpha expression inversely correlated with neutral lipid accumulation, which was more prominent at the alveolar base, distant from the AER. PDGF-Ralpha-expressing alveolar cells accumulate in the AER where they may promote mechanical stability during respiration. In addition to defining how alveolar septa form, these findings may have implications for the treatment of diseases which involve alveolar effacement such as emphysema and pulmonary fibrosis.
authors.affiliation: Research Service, Iowa City Department of Veterans Affairs Medical Center, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA. stephen-mcgowan@uiowa.edu
authors.forename: Stephen E
authors.initials: SE
authors.lastname: McGowan
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Grossmann
authors.forename: Patricia W
authors.initials: PW
authors.lastname: Kimani
authors.forename: Amey J
authors.initials: AJ
authors.lastname: Holmes
mesh_terms: D000199:Actins / Q000378:metabolism; D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000502:physiology; D004549:Elastin / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D007150:Immunohistochemistry; D008055:Lipids / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D038081:Organogenesis / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism*; D012143:Respiratory Physiological Phenomena
chemical_list: D000199:Actins; D008055:Lipids; D010982:Platelet-Derived Growth Factor; C075278:platelet-derived growth factor A; D004549:Elastin; D020796:Receptor, Platelet-Derived Growth Factor alpha