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

H Boström; K Willetts; M Pekny; P Levéen; P Lindahl; H Hedstrand; M Pekna; M Hellström; S Gebre-Medhin; M Schalling; M Nilsson; S Kurland; J Törnell; J K Heath; C Betsholtz

doi:10.1016/s0092-8674(00)81270-2

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

Cell. 1996 Jun 14;85(6):863-73. doi: 10.1016/s0092-8674(00)81270-2.

Authors

H Boström¹, K Willetts, M Pekny, P Levéen, P Lindahl, H Hedstrand, M Pekna, M Hellström, S Gebre-Medhin, M Schalling, M Nilsson, S Kurland, J Törnell, J K Heath, C Betsholtz

Affiliation

¹ Department of Medical Biochemistry, University of Göteborg, Sweden.

PMID: 8681381
DOI: 10.1016/s0092-8674(00)81270-2

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.

Publication types

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

MeSH terms

Actins / analysis
Animals
Cardiomegaly / pathology
Chimera
Crosses, Genetic
Elastin / analysis
Fibroblasts / cytology
Fibroblasts / pathology
Gene Targeting
Lung / embryology
Lung / ultrastructure
Mice
Mice, Mutant Strains
Muscle, Smooth / chemistry
Muscle, Smooth / cytology
Phenotype
Platelet-Derived Growth Factor / deficiency
Platelet-Derived Growth Factor / genetics
Platelet-Derived Growth Factor / physiology*
Pulmonary Alveoli / chemistry
Pulmonary Alveoli / cytology
Pulmonary Alveoli / growth & development*
Pulmonary Alveoli / pathology
Pulmonary Emphysema / pathology*
RNA, Messenger / analysis
Receptor, Platelet-Derived Growth Factor alpha
Receptors, Platelet-Derived Growth Factor / analysis
Signal Transduction / physiology

Substances

Actins
Platelet-Derived Growth Factor
RNA, Messenger
platelet-derived growth factor A
Elastin
Receptor, Platelet-Derived Growth Factor alpha
Receptors, Platelet-Derived Growth Factor