Platelet-derived growth factor-A and sonic hedgehog signaling direct lung fibroblast precursors during alveolar septal formation

Stephen E McGowan; Diann M McCoy

doi:10.1152/ajplung.00011.2013

Back

Platelet-derived growth factor-A and sonic hedgehog signaling direct lung fibroblast precursors during alveolar septal formation

Journal article

Open access

Peer reviewed

Platelet-derived growth factor-A and sonic hedgehog signaling direct lung fibroblast precursors during alveolar septal formation

Stephen E McGowan and Diann M McCoy

American journal of physiology. Lung cellular and molecular physiology, Vol.305(3), pp.L229-L239

08/01/2013

DOI: 10.1152/ajplung.00011.2013

PMID: 23748534

Files and links (1)

url

https://doi.org/10.1152/ajplung.00011.2013View

Published (Version of record) Open Access

Abstract

Alveolar septal formation is required to support the respiration of growing mammals; in humans effacement of the alveolar surface and impaired gas exchange are critical features of emphysema and pulmonary fibrosis. Platelet-derived growth factor-A (PDGF-A) and its receptor PDGF-receptor-α (PDGFRα) are required for secondary septal elongation in mice during postnatal days 4 through 12 and they regulate the proliferation and septal location of interstitial fibroblasts. We examined lung fibroblasts (LF) to learn whether PDGFRα expression distinguished a population of precursor cells, with enhanced proliferative and migratory capabilities. We identified a subpopulation of LF that expresses sonic hedgehog (Shh) and stem cell antigen-1 (Sca1). PDGF-A and Shh both increased cytokinesis and chemotaxis in vitro, but through different mechanisms. In primary LF cultures, Shh signaled exclusively through a noncanonical pathway involving generation of Rac1-GTP, whereas both the canonical and noncanonical pathways were used by the Mlg neonatal mouse LF cell line. LF preferentially oriented their primary cilia toward their anterior pole during migration. Furthermore, a larger proportion of PDGFRα-expressing LF, which are more abundant at the septal tips, bore primary cilia compared with other alveolar cells. In pulmonary emphysema, destroyed alveolar septa do not regenerate, in part because cells fail to assume a configuration that allows efficient gas exchange. Better understanding how LF are positioned during alveolar development could identify signaling pathways, which promote alveolar septal regeneration.

Antigens, CD34 - analysis

Cell Proliferation

Hedgehog Proteins - metabolism

Membrane Proteins - analysis

Actins - analysis

Neuropeptides - biosynthesis

Pulmonary Alveoli - metabolism

Pulmonary Alveoli - cytology

Lung - metabolism

Fibroblasts - metabolism

Cell Line

Receptor, Platelet-Derived Growth Factor alpha - metabolism

Signal Transduction

Hedgehog Proteins - analysis

Mice, Transgenic

Neuropeptides - metabolism

Antigens, Ly - analysis

Platelet-Derived Growth Factor - metabolism

Animals

Ki-67 Antigen - analysis

Lung - embryology

Mice

rac1 GTP-Binding Protein - biosynthesis

Pulmonary Alveoli - embryology

rac1 GTP-Binding Protein - metabolism

Cell Movement

Details

Title: Subtitle: Platelet-derived growth factor-A and sonic hedgehog signaling direct lung fibroblast precursors during alveolar septal formation
Creators: Stephen E McGowan - Department of Veterans Affairs Research Service, Iowa City, IA, USA. stephen-mcgowan@uiowa.edu
Diann M McCoy
Resource Type: Journal article
Publication Details: American journal of physiology. Lung cellular and molecular physiology, Vol.305(3), pp.L229-L239
DOI: 10.1152/ajplung.00011.2013
PMID: 23748534
NLM abbreviation: Am J Physiol Lung Cell Mol Physiol
ISSN: 1040-0605
eISSN: 1522-1504
Publisher: United States
Grant note: I01 BX000508 / BLRD VA
Language: English
Date published: 08/01/2013
Academic Unit: International Programs; Internal Medicine
Record Identifier: 9983983664802771

Metrics

30 Record Views

42 Times Cited - Web of Science