title: PDGF-A signaling is a critical event in lung alveolar myofibroblast development and alveogenesis.
abstract: A mouse platelet-derived growth factor A chain (PDGF-A) null allele is shown to be homozygous lethal, with two distinct restriction points, one prenatally before E10 and one postnatally. Postnatally surviving PDGF-A-deficient mice develop lung emphysema secondary to the failure of alveolar septation. This is apparently caused by the loss of alveolar myofibroblasts and associated elastin fiber deposits. PDGF alpha receptor-positive cells in the lung having the location of putative alveolar myofibroblast progenitors were specifically absent in PDGF-A null mutants. We conclude that PDGF-A is crucial for alveolar myofibroblast ontogeny. We have previously shown that PDGF-B is required in the ontogeny of kidney mesangial cells. The PDGFs therefore appear to regulate the generation of specific populations of myofibroblasts during mammalian development. The two PDGF null phenotypes also reveal analogous morphogenetic functions for myofibroblast-type cells in lung and kidney organogenesis.
authors.affiliation: Department of Medical Biochemistry, University of Göteborg, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Boström
authors.forename: K
authors.initials: K
authors.lastname: Willetts
authors.forename: M
authors.initials: M
authors.lastname: Pekny
authors.forename: P
authors.initials: P
authors.lastname: Levéen
authors.forename: P
authors.initials: P
authors.lastname: Lindahl
authors.forename: H
authors.initials: H
authors.lastname: Hedstrand
authors.forename: M
authors.initials: M
authors.lastname: Pekna
authors.forename: M
authors.initials: M
authors.lastname: Hellström
authors.forename: S
authors.initials: S
authors.lastname: Gebre-Medhin
authors.forename: M
authors.initials: M
authors.lastname: Schalling
authors.forename: M
authors.initials: M
authors.lastname: Nilsson
authors.forename: S
authors.initials: S
authors.lastname: Kurland
authors.forename: J
authors.initials: J
authors.lastname: Törnell
authors.forename: J K
authors.initials: JK
authors.lastname: Heath
authors.forename: C
authors.initials: C
authors.lastname: Betsholtz
mesh_terms: D000199:Actins / Q000032:analysis; D000818:Animals; D006332:Cardiomegaly / Q000473:pathology; D002678:Chimera; D003433:Crosses, Genetic; D004549:Elastin / Q000032:analysis; D005347:Fibroblasts / Q000166:cytology / Q000473:pathology; D018390:Gene Targeting; D008168:Lung / Q000196:embryology / Q000648:ultrastructure; D051379:Mice; D008817:Mice, Mutant Strains; D009130:Muscle, Smooth / Q000737:chemistry / Q000166:cytology; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011650:Pulmonary Alveoli / Q000737:chemistry / Q000166:cytology / Q000254:growth & development* / Q000473:pathology; D011656:Pulmonary Emphysema / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D020796:Receptor, Platelet-Derived Growth Factor alpha; D017479:Receptors, Platelet-Derived Growth Factor / Q000032:analysis; D015398:Signal Transduction / Q000502:physiology
chemical_list: D000199:Actins; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; C075278:platelet-derived growth factor A; D004549:Elastin; D020796:Receptor, Platelet-Derived Growth Factor alpha; D017479:Receptors, Platelet-Derived Growth Factor