A critical role for fibroblast growth factor-7 during early alveolar formation in the neonatal rat.
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.
Padela
Sanna
S
Department of Physiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Yi
Man
M
Cabacungan
Judy
J
Shek
Samuel
S
Belcastro
Rosetta
R
Masood
Azhar
A
Jankov
Robert P
RP
Tanswell
A Keith
AK
D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000008:administration & dosage; D000918:Antibody Specificity; D049109:Cell Proliferation; D004261:DNA Replication; D042783:Endothelial Cells / Q000378:metabolism*; D051523:Fibroblast Growth Factor 7 / Q000276:immunology / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D007274:Injections, Intraperitoneal; D011650:Pulmonary Alveoli / Q000098:blood supply / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D051381:Rats; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D000906:Antibodies; C496455:Fgf7 protein, rat; D017468:Receptors, Fibroblast Growth Factor; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D051523:Fibroblast Growth Factor 7; D017228:Hepatocyte Growth Factor; D040301:Vascular Endothelial Growth Factor Receptor-2