Fibroblast growth factor 23 and Klotho contribute to airway inflammation

The European Respiratory Journal
Stefanie KrickMatthias Salathe

Abstract

Circulating levels of fibroblast growth factor (FGF)23 are associated with systemic inflammation and increased mortality in chronic kidney disease. α-Klotho, a co-receptor for FGF23, is downregulated in chronic obstructive pulmonary disease (COPD). However, whether FGF23 and Klotho-mediated FGF receptor (FGFR) activation delineates a pathophysiological mechanism in COPD remains unclear. We hypothesised that FGF23 can potentiate airway inflammation via Klotho-independent FGFR4 activation.FGF23 and its effect were studied using plasma and transbronchial biopsies from COPD and control patients, and primary human bronchial epithelial cells isolated from COPD patients as well as a murine COPD model.Plasma FGF23 levels were significantly elevated in COPD patients. Exposure of airway epithelial cells to cigarette smoke and FGF23 led to a significant increase in interleukin-1β release via Klotho-independent FGFR4-mediated activation of phospholipase Cγ/nuclear factor of activated T-cells signalling. In addition, Klotho knockout mice developed COPD and showed airway inflammation and elevated FGFR4 expression in their lungs, whereas overexpression of Klotho led to an attenuation of airway inflammation.Cigarette smoke induces airway infla...Continue Reading

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Citations

May 12, 2019·International Journal of Molecular Sciences·Swati GulatiStefanie Krick
Nov 2, 2018·International Journal of Molecular Sciences·Jaleesa GarthStefanie Krick
Apr 12, 2019·Frontiers in Physiology·Annelies J van VurenEduard J van Beers
Jan 23, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Sanja BlaskovicConstance Barazzone-Argiroffo
Sep 25, 2020·International Journal of Molecular Sciences·Molly EasterStefanie Krick
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May 2, 2019·American Journal of Physiology. Lung Cellular and Molecular Physiology·Jarrod W BarnesStefanie Krick
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