Journal article
Effect of tyrosine kinase inhibition on surfactant protein A gene expression during human lung development
American journal of physiology. Lung cellular and molecular physiology, Vol.274(4), pp.L542-L551
04/01/1998
DOI: 10.1152/ajplung.1998.274.4.L542
PMID: 9575872
Abstract
Epidermal growth factor (EGF) stimulates surfactant protein (SP) A synthesis in human fetal lung explants. Ligand binding to the EGF receptor stimulates an intrinsic receptor tyrosine kinase with subsequent activation of second messengers. We hypothesized that inhibition of EGF-receptor tyrosine kinase activity would block SP-A expression in spontaneously differentiating cultured human fetal lung tissue. Midtrimester fetal lung explants were exposed for 4 days to genistein (a broad-range inhibitor of tyrosine kinases) and tyrphostin AG-1478 (a specific inhibitor of EGF-receptor tyrosine kinase). Genistein significantly decreased SP-A and SP-A mRNA levels without affecting either tissue viability or the morphological differentiation of alveolar type II cells. Tyrphostin AG-1478 also decreased SP-A content and SP-A mRNA levels in cultured fetal lung explants. Treatment with EGF could not overcome the inhibitory effects of either genistein or tyrphostin on SP-A; however, only tyrphostin inhibited EGF-receptor tyrosine phosphorylation. We conclude that specific inhibition of EGF-receptor tyrosine kinase with tyrphostin AG-1478 blocks the expression of SP-A during spontaneous differentiation of cultured human fetal lung tissue. Furthermore, exposure to genistein also decreases SP-A expression and blocks the effects of EGF in human fetal lung tissue without inhibiting EGF-receptor tyrosine phosphorylation. These findings support the importance of tyrosine kinase-dependent signal transduction pathways in the regulation of SP-A during human fetal lung development.
Details
- Title: Subtitle
- Effect of tyrosine kinase inhibition on surfactant protein A gene expression during human lung development
- Creators
- Jonathan M Klein - Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242-1083Louis J Dewild - Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242-1083Troy A McCarthy - Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242-1083
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Lung cellular and molecular physiology, Vol.274(4), pp.L542-L551
- DOI
- 10.1152/ajplung.1998.274.4.L542
- PMID
- 9575872
- ISSN
- 1040-0605
- eISSN
- 1522-1504
- Language
- English
- Date published
- 04/01/1998
- Academic Unit
- Stead Family Department of Pediatrics; Neonatology
- Record Identifier
- 9984093600202771
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