Journal article
Fibroblast growth factor signaling in myofibroblasts differs from lipofibroblasts during alveolar septation in mice
American journal of physiology. Lung cellular and molecular physiology, Vol.309(5), pp.L463-L474
09/01/2015
DOI: 10.1152/ajplung.00013.2015
PMCID: PMC4556933
PMID: 26138642
Abstract
Pulmonary alveolar fibroblasts produce extracellular matrix in a temporally and spatially regulated pattern to yield a durable yet pliable gas-exchange surface. Proliferation ensures a sufficient complement of cells, but they must differentiate into functionally distinct subtypes: contractile myofibroblasts (MF), which generate elastin and regulate air-flow at the alveolar ducts, and, in mice and rats, lipofibroblasts (LF), which store neutral lipids. PDGF-A is required but acts in conjunction with other differentiation factors arising from adjacent epithelia or within fibroblasts. We hypothesized that FGF receptor (FGFR) expression and function vary for MF and LF and contributes to their divergent differentiation. Whereas approximately half of the FGFR3 was extracellular in MF, FGFR2 and FGFR4 were primarily intracellular. Intracellular FGFR3 localized to the multivesicular body, and its abundance may be modified by Sprouty and interaction with heat shock protein-90. FGF18 mRNA is more abundant in MF, whereas FGF10 mRNA predominated in LF, which also express FGFR1 IIIb, a receptor for FGF10. FGF18 diminished fibroblast proliferation and was chemotactic for cultured fibroblasts. Although PDGF receptor-α (PDGFR-α) primarily signals through phosphoinositide 3-kinase and Akt, p42/p44 MAP kinase (Erk1/2), a major signaling pathway for FGFRs, influenced the abundance of cell-surface PDGFR-α. Observing different FGFR and ligand profiles in MF and LF is consistent with their divergent differentiation although both subpopulations express PDGFR-α. These studies also emphasize the importance of particular cellular locations of FGFR3 and PDGFR-α, which may modify their effects during alveolar development or repair.
Details
- Title: Subtitle
- Fibroblast growth factor signaling in myofibroblasts differs from lipofibroblasts during alveolar septation in mice
- Creators
- Stephen E McGowan - Department of Veterans Affairs Research Service and Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa stephen-mcgowan@uiowa.eduDiann M McCoy - Department of Veterans Affairs Research Service and Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Lung cellular and molecular physiology, Vol.309(5), pp.L463-L474
- Publisher
- United States
- DOI
- 10.1152/ajplung.00013.2015
- PMID
- 26138642
- PMCID
- PMC4556933
- ISSN
- 1040-0605
- eISSN
- 1522-1504
- Grant note
- 1S10 RR027219 / NCRR NIH HHS I01 BX000508 / BLRD VA
- Language
- English
- Date published
- 09/01/2015
- Academic Unit
- International Programs; Internal Medicine
- Record Identifier
- 9983983669302771
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