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 FGFR activation delineates a pathophysiologic mechanism in COPD remains unclear. We hypothesized 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 IL-1β release via klotho-independent FGFR4-mediated activation of phospholipase Cγ(PLCγ)/nuclear factor of activated T-cells (NFAT) signaling. 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.In conclusion, cigarette smoke induces airway inflammation by downregulation of klotho and activation of FGFR4 in the airway epithelium in COPD. Inhibition of FGF23 or FGFR4 might serve as a novel anti-inflammatory strategy in COPD.
Pharmacology, Toxicology and Pharmaceutical Science
4
9%
Immunology and Microbiology
3
6%
Biochemistry, Genetics and Molecular Biology
2
4%
Nursing and Health Professions
1
2%
Other
3
6%
Unknown
25
53%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 26 January 2019.
All research outputs
#7,597,666
of 23,306,612 outputs
Outputs from European Respiratory Journal
#4,473
of 8,795 outputs
Outputs of similar age
#129,450
of 326,690 outputs
Outputs of similar age from European Respiratory Journal
#84
of 119 outputs
Altmetric has tracked 23,306,612 research outputs across all sources so far. This one has received more attention than most of these and is in the 67th percentile.
So far Altmetric has tracked 8,795 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 14.8. This one is in the 48th percentile – i.e., 48% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 326,690 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 60% of its contemporaries.
We're also able to compare this research output to 119 others from the same source and published within six weeks on either side of this one. This one is in the 30th percentile – i.e., 30% of its contemporaries scored the same or lower than it.
