Am. J. Respir. Cell Mol. Biol., Volume 19, Number 4, October, 1998 563-572

Differential Expression of Fibroblast Growth Factor Receptors 1 to 4 and Ligand Genes in Late Fetal and Early Postnatal Rat Lung

Penelope P. Powell, Chi-Chung Wang, Hirohisa Horinouchi, Kenneth Shepherd, Margaretha Jacobson, Marcia Lipson, and Rosemary Jones

Molecular and Cell Biology Laboratory, Department of Anaesthesia and Critical Care Medicine, Massachusetts General HospitalEast; Department of Anaesthesia, Harvard Medical School, Boston, Massachusetts; Department of Immunology and Pathology, BBSRC Institute for Animal Health, Pirbright, Surrey, United Kingdom; Division of Thoracic Surgery, Department of Surgery, Keio University School of Medicine, Shinjuku Tokyo, Japan

To characterize fibroblast growth factor (FGF) gene expression in the late fetal (days E18 to E22) and early postnatal lung (days P0 to P28), when the alveolar region undergoes extensive growth and reorganization, we analyzed the expression of four FGF receptors and six ligands. FGF receptor 1 (FGFR1) RNA levels were first low (E18) before rising late in the postnatal period (P28). FGFR2 RNA levels were detected early (at E18) and then increased (E20-P0) before falling (P2) to below later postnatal levels (P6 to P28). FGFR3 RNA levels were low at first (E18) and then increased, with peak levels in the days after birth (P2 to P10). FGFR4 RNA levels, barely detected in fetal lung (E18 to E22), increased at birth (P0) and remained high postnatally (P2 to P28). In fetal lung, FGF2 (basic FGF) RNA expression levels were low and FGF1 (acidic FGF) RNA levels were not detected: low RNA levels of each ligand were detected postnatally (P7 to P28). FGF3 to 5 and FGF7 RNA were not detected in fetal or postnatal lung. With in situ hybridization, predominantly the smooth muscle cells of large vessels expressed FGFR1 and 4 mRNA; the epithelial cells of large airways expressed FGFR1, 2, and 4; and alveolar cells expressed FGFR2, 3, and 4. Analysis of protein expression first identified FGF2 localized to the basement membrane of large airways and branching epithelial buds, to mesenchymal cells associated with buds, to the putative smooth muscle cells of large airways and vessels, and to pleural- and mesenchymal-associated cells (E18). Immediately before birth, this pattern of expression persisted (E20 to E22), with FGF2 also being expressed by putative smooth muscle cells of smaller airways and vessels (E22). After birth (P0 to P28), FGF2 expression remained relatively high in the smooth muscle cells of large and small vessels and in pleural cells; in airway smooth muscle cells and in most cells in the alveolar region, however, although FGF2 expression persisted in some cells, its intensity decreased with time.

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