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PDGF-A signaling is...
PDGF-A signaling is required for secondary alveolar septation and controls epithelial proliferation in the developing lung
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- Gouveia, Leonor (author)
- Uppsala universitet,Vaskulärbiologi,Christer Betsholtz
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- Betsholtz, Christer (author)
- Karolinska Institutet,Uppsala universitet,Vaskulärbiologi
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- Andrae, Johanna (author)
- Uppsala universitet,Vaskulärbiologi
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(creator_code:org_t)
- 2018-04-10
- 2018
- English.
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In: Development. - : The Company of Biologists. - 0950-1991 .- 1477-9129. ; 145:7
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Abstract
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- Platelet-derived growth factor A (PDGF-A) signaling through PDGF receptor a is essential for alveogenesis. Previous studies have shown that Pdgfa(-/-) mouse lungs have enlarged alveolar airspace with absence of secondary septation, both distinctive features of bronchopulmonary dysplasia. To study how PDGF-A signaling is involved in alveogenesis, we generated lung-specific Pdgfa knockout mice (Pdgfa(fl/-); Spc-cre) and characterized their phenotype postnatally. Histological differences between mutant mice and littermate controls were visible after the onset of alveogenesis and maintained until adulthood. Additionally, we generated Pdgfa(fl/-); Spc-cre; Pdgfra(GFP/+) mice in which Pdgfra(+) cells exhibit nuclear GFP expression. In the absence of PDGF-A, the number of Pdgfra(GFP+) cells was significantly decreased. In addition, proliferation of Pdgfra(GFP+) cells was reduced. During alveogenesis, Pdgfra(GFP+) myofibroblasts failed to form the alpha-smooth muscle actin rings necessary for alveolar secondary septation. These results indicate that PDGF-A signaling is involved in myofibroblast proliferation and migration. In addition, we show an increase in both the number and proliferation of alveolar type II cells in Pdgfa(fl/-); Spc-cre lungs, suggesting that the increased alveolar airspace is not caused solely by deficient myofibroblast function.
Subject headings
- NATURVETENSKAP -- Biologi -- Utvecklingsbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Developmental Biology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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