Journal article
Neuregulin-1 and human epidermal growth factor receptors 2 and 3 play a role in human lung development in vitro
American journal of respiratory cell and molecular biology, Vol.22(4), pp.432-440
04/2000
DOI: 10.1165/ajrcmb.22.4.3854
PMID: 10745024
Abstract
The human epidermal growth factor receptor (HER) family consists of four distinct receptors: HER1 (epidermal growth factor receptor), HER2, HER3, and HER4. Their specific activating ligands are collectively known as neuregulins (NRG). We hypothesized that one member of the NRG family, NRG-1, and the HER family would play a role in fetal lung development. To test this hypothesis, we defined NRG-1 and HER gene expression in mid-trimester human fetal lung tissue. HER2 and HER3 messenger RNA and protein were detected in the fetal lung, but HER4 expression was not detected. Immunohistochemical staining of fetal lung tissue localized HER2 and HER3 protein to the developing lung epithelium. NRG-1 expression was not found in freshly isolated human fetal lung, but it was observed in fetal lung explants after 2 d of explant culture. Immunohistochemistry of cultured human fetal lung explants revealed that NRG-1 protein was also expressed in pulmonary epithelial cells. Exposing human fetal lung to recombinant NRG-1 activated the HER receptor complex as measured by approximately 4-fold increases in receptor phosphotyrosine content. In addition, NRG-1 increased explant epithelial cell volume density approximately 2-fold (P < 0. 03); increased epithelial cell proliferation approximately 2-fold, as determined by bromodeoxyuridine labeling (P = 0.002); and reduced surfactant protein-A (SP-A) levels by 53% (P < 0.05). These data are consistent with an autocrine regulatory process mediated by NRG-1 activation of HER2/HER3 heterodimers expressed on developing human fetal lung epithelial cells. Receptor activation results in increased lung epithelial cell proliferation and volume density, and decreased SP-A production, a marker of type II pneumocyte differentiation.
Details
- Title: Subtitle
- Neuregulin-1 and human epidermal growth factor receptors 2 and 3 play a role in human lung development in vitro
- Creators
- N V Patel - Departments of Internal Medicine, Pediatrics, and Anatomy and Cell Biology, University of Iowa College of Medicine, Iowa City, IA 52242, USAM J AcarreguiJ M SnyderJ M KleinM X SliwkowskiJ A Kern
- Resource Type
- Journal article
- Publication Details
- American journal of respiratory cell and molecular biology, Vol.22(4), pp.432-440
- DOI
- 10.1165/ajrcmb.22.4.3854
- PMID
- 10745024
- ISSN
- 1044-1549
- eISSN
- 1535-4989
- Language
- English
- Date published
- 04/2000
- Academic Unit
- Anatomy and Cell Biology; Stead Family Department of Pediatrics; Neonatology
- Record Identifier
- 9984093365602771
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