PDGF-A signaling is a critical event in lung alveolar myofibroblast development and alveogenesis.

• 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.

Nyckelord

Actins/analysis

Animals

Cardiomegaly/pathology

Chimera

Crosses; Genetic

Elastin/analysis

Fibroblasts/cytology/pathology

Gene Targeting

Lung/embryology/ultrastructure

Mice

Mice; Mutant Strains

Muscle; Smooth/chemistry/cytology

Phenotype

Platelet-Derived Growth Factor/deficiency/genetics/*physiology

Pulmonary Alveoli/chemistry/cytology/*growth & development/pathology

Pulmonary Emphysema/*pathology

RNA; Messenger/analysis

Receptor; Platelet-Derived Growth Factor alpha

Receptors; Platelet-Derived Growth Factor/analysis

Research Support; Non-U.S. Gov't

Signal Transduction/physiology

Publikations- och innehållstyp

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