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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1999-8-3
pubmed:abstractText
Fibroblast growth factors (FGFs) play important roles in diverse aspects of animal development including mammalian lung epithelial cell proliferation, differentiation, and branching morphogenesis. We developed an in vitro lung epithelial cell culture system to study functions and mechanisms of FGFs in regulating growth and differentiation of primary foetal rat lung epithelial cells. In comparison with other growth factors such as IGF-I, EGF, and HGF, FGFs were the most potent mitogens in stimulating lung epithelial cell proliferation. In the presence of FGF-1, 2, or 7, the primary lung epithelial cells could be propagated for generations and grown for more than two mo in vitro. Among the three FGFs tested, FGF-7 showed the strongest stimulation in cell growth. FGF-2, on the other hand, is the most effective inducer of lung epithelial cell-specific surfactant protein gene expression (SP-A, -B, and -C). FGF-2 upregulated SP-C expression in a dose-dependent manner. More interestingly, the induction of surfactant protein gene expression by FGF-2 appeared to be independent of MAPK pathway, since the SP-C expression was not inhibited but rather augmented by MEK1 inhibitor which inhibited MAPK activation and cell proliferation. Similar effects were observed for the expressions of surfactant protein genes SP-A and SP-B. In contrast to MAPK, FGF-2-induced SP-C expression was partially inhibited by PI 3-kinase inhibitor wortmannin. These data suggest dynamic roles and complex signalling mechanisms of FGFs in regulating lung epithelial cell proliferation and differentiation. While a MAPK-dependent pathway is essential for all three FGFs to stimulate cell proliferation, a MAPK-independent pathway may be responsible for the FGF-2-induced surfactant protein gene expression. PI 3-kinase may play an important role in mediating FGF-2-induced lung epithelial cell differentiation during development.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0898-6568
pubmed:author
pubmed:issnType
Print
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
221-8
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
FGF-2 induces surfactant protein gene expression in foetal rat lung epithelial cells through a MAPK-independent pathway.
pubmed:affiliation
Pulmonary Center, Department of Medicine, Boston University Medical Center, MA 02118, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.