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Published on: January 7, 2016
A critical role for fibroblast growth factor-7 during early alveolar formation in the neonatal rat
Sanna Padela1, Man Yi, Judy Cabacungan
1Department of Physiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Insights
Fibroblast growth factor-7 (FGF-7) is crucial for early lung development in neonatal rats. Inhibiting FGF-7 impaired alveolar formation and reduced blood vessel growth, highlighting its role in vascular development.
Area of Science:
- Pulmonology
- Developmental Biology
- Cell Biology
Background:
- Mesenchymal cell-derived fibroblast growth factor-7 (FGF-7) promotes epithelial and endothelial cell proliferation.
- FGF-7 is expressed in neonatal rat lungs from birth to 14 days.
- Previous studies excluded a role for FGF-7 in alveolar formation via type II pneumocytes.
Purpose of the Study:
- To investigate the role of FGF-7 in early postnatal lung alveolar formation.
- To determine if FGF-7 influences cell types other than type II pneumocytes in lung development.
Main Methods:
- Administered intraperitoneal injections of neutralizing antibodies against FGF-7 on days 3, 4, and 5 of life in neonatal rats.
- Assessed alveolar formation and secondary crest development on day 6 of life.
- Quantified DNA synthesis and the number of alveoli-forming secondary crests and peripheral blood vessels.
Main Results:
- FGF-7 inhibition significantly reduced DNA synthesis and the number of alveoli-forming secondary crests.
- A significant decrease in the overall alveolar number was observed following FGF-7 inhibition.
- Reduced alveolar formation was correlated with a decrease in the number of small peripheral lung blood vessels.
Conclusions:
- FGF-7 is essential for normal early postnatal alveolar formation from secondary crests.
- FGF-7 likely exerts its effect on alveolar formation through its influence on the lung's vascular bed.
- The vascular effects of FGF-7 are critical for proper lung development in early life.
Abstract:
Mesenchymal cell-derived FGF-7 (fibroblast growth factor-7) induces proliferation in both epithelial and endothelial cells. We found FGF-7 to be expressed in the lungs of neonatal rats from birth to d 14 of age. A role for FGF-7 in early postnatal lung growth and alveolar formation, by an action on type II pneumocytes, has been excluded by the work of others. However, a role through an action of FGF-7 on other cell types has not been excluded. We used intraperitoneal injections of neutralizing antibodies on d 3, 4, and 5 of life to inhibit binding of FGF-7 to its receptors, and assessed alveolar formation on d 6 of life. This intervention inhibited DNA synthesis in, and number of, alveoli-forming secondary crests, resulting in a significantly reduced alveolar number. This failure of alveolar formation was associated with a reduction in the number of small blood vessels in the lung periphery. We conclude that FGF-7, most likely through its effect on the vascular bed, is required for normal early postnatal alveolar formation from secondary crests.
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