Journalartikel

Jahr der Veröffentlichung: 2018

Seiten: L248-L252

Zeitschrift: American Journal of Physiology - Lung Cellular and Molecular Physiology

Bandnummer: 315

Heftnummer: 2

ISSN: 1040-0605

eISSN: 1522-1504

Open Access Status: Bronze

DOI Link: https://doi.org/10.1152/ajplung.00140.2018

Verlag: American Physiological Society

Abstract: 
Idiopathic pulmonary arterial hypertension (IPAH), pulmonary hypertension (PH) due to lung disease and/or hypoxia and idiopathic pulmonary fibrosis (IPF) are increasingly recognized as important contributors to mortality and morbidity worldwide. Among others, the current treatment paradigm considers broad inhibition of receptor tyrosine kinases, a strategy that likely leads to collateral inhibition of signaling pathways that are critical for lung repair and regeneration. Fibroblast growth factor 7 (FGF7) and FGF10 signaling in the lung through FGF receptor 2 (FGFR2) are involved in epithelial cell protection and renewal, and mutations in their corresponding genes in humans are linked to increased susceptibility to lung pathologies, such as chronic obstructive pulmonary disease and bronchopulmonary dysplasia. In this report, we present data demonstrating significant upregulation of FGF7, FGF10, and FGFR2 in IPF and IPAH lungs compared with donor lungs. These ligands and their cognate receptor converged on the remodeled parenchyma and vasculature of IPF and IPAH lungs. Interestingly, the expression levels of FGFR1, which has been previously shown to play a pathological role in PH development, were not significantly changed in either disease state. Intriguingly, the expression levels of FGF7, FGF10, and FGFR2 were lower in IPF lung regions undergoing active remodeling, and inversely correlated with IPAH severity, indicating that increased expression might reflect lung repair rather than lung pathology, and warranting further research on the precise role of FGF signaling in pulmonary parenchymal and vascular remodeling.

Harvard-Zitierstil: El Agha, E., Schwind, F., Ruppert, C., Guenther, A., Bellusci, S., Schermuly, R., et al. (2018) Is the fibroblast growth factor signaling pathway a victim of receptor tyrosine kinase inhibition in pulmonary parenchymal and vascular remodeling?, American Journal of Physiology - Lung Cellular and Molecular Physiology, 315(2), pp. L248-L252. https://doi.org/10.1152/ajplung.00140.2018

APA-Zitierstil: El Agha, E., Schwind, F., Ruppert, C., Guenther, A., Bellusci, S., Schermuly, R., & Kosanovic, D. (2018). Is the fibroblast growth factor signaling pathway a victim of receptor tyrosine kinase inhibition in pulmonary parenchymal and vascular remodeling?. American Journal of Physiology - Lung Cellular and Molecular Physiology. 315(2), L248-L252. https://doi.org/10.1152/ajplung.00140.2018