Publication: Fibroblast growth factor receptors control epithelial-mesenchymal interactions necessary for alveolar elastogenesis
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Issued Date
2010-04-15
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ISSN
15354970
1073449X
1073449X
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2-s2.0-77953045672
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Mahidol University
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SCOPUS
Bibliographic Citation
American Journal of Respiratory and Critical Care Medicine. Vol.181, No.8 (2010), 838-850
Suggested Citation
Sorachai Srisuma, Soumyaroop Bhattacharya, Dawn M. Simon, Siva K. Solleti, Shivraj Tyagi, Barry Starcher, Thomas J. Mariani Fibroblast growth factor receptors control epithelial-mesenchymal interactions necessary for alveolar elastogenesis. American Journal of Respiratory and Critical Care Medicine. Vol.181, No.8 (2010), 838-850. doi:10.1164/rccm.200904-0544OC Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/29703
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Title
Fibroblast growth factor receptors control epithelial-mesenchymal interactions necessary for alveolar elastogenesis
Abstract
Rationale: The mechanisms contributing to alveolar formation are poorly understood. A better understanding of these processes will improve efforts to ameliorate lung disease of the newborn and promote alveolar repair in the adult. Previous studies have identified impaired alveogenesis in mice bearing compound mutations of fibroblast growth factor (FGF) receptors (FGFRs) 3 and 4, indicating that these receptors cooperatively promote postnatal alveolar formation. Objectives: To determine the molecular and cellular mechanisms of FGF-mediated alveolar formation. Methods: Compound FGFR3/FGFR4-deficient mice were assessed for temporal changes in lung growth, airspace morphometry, and genome-wide expression. Observed gene expression changes were validated using quantitative real-time RT-PCR, tissue biochemistry, histochemistry, and ELISA. Autocrine and paracrine regulatory mechanisms were investigated using isolated lung mesenchymal cells and type II pneumocytes. Measurements and Main Results: Quantitative analysis of airspace ontogeny confirmed a failure of secondary crest elongation in compound mutant mice. Genome-wide expression profiling identified molecular alterations in these mice involving aberrant expression of numerous extracellular matrix molecules. Biochemical and histochemical analysis confirmed changes in elastic fiber gene expression resulted in temporal increases in elastin deposition with the loss of typical spatial restriction. No abnormalities in elastic fiber gene expression were observed in isolated mesenchymal cells, indicating that abnormal elastogenesis in compound mutant mice is not cell autonomous. Increased expression of paracrine factors, including insulin-like growth factor21, in freshly-isolated type II pneumocytes indicated that these cells contribute to the observed pathology. Conclusions: Epithelial/mesenchymal signaling mechanisms appear to contribute to FGFR-dependent alveolar elastogenesis and proper airspace formation.