Fibroblast Growth Factor Receptor 4 Deficiency Mediates Airway Inflammation in the Adult Healthy Lung? Article Swipe
Molly Easter
,
Jaleesa M. Garth
,
Elex S. Harris
,
Ren‐Jay Shei
,
E. Scott Helton
,
Yuhua Wei
,
Rebecca Denson
,
Rennan Zaharias
,
Steven M. Rowe
,
Patrick Geraghty
,
Christian Faul
,
Jarrod W. Barnes
,
Stefanie Krick
·
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.3389/fmed.2020.00317
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.3389/fmed.2020.00317
Fibroblast growth factor receptor (FGFR) 4 has been shown to mediate pro-inflammatory signaling in the liver and airway epithelium in chronic obstructive pulmonary disease. In past reports, FGFR4 knockout (Fgfr4 -/- ) mice did not show any lung phenotype developmentally or at birth, unless FGFR3 deficiency was present simultaneously. Therefore, we wanted to know whether the loss of FGFR4 had any effect on the adult murine lung. Our results indicate that adult Fgfr4 -/- mice demonstrate a lung phenotype consisting of widened airway spaces, increased airway inflammation, bronchial obstruction, and right ventricular hypertrophy consistent with emphysema. Despite downregulation of FGF23 serum levels, interleukin (IL) 1β and IL-6 in the Fgfr4 -/- lung, and abrogation of p38 signaling, primary murine Fgfr4 -/- airway cells showed increased expression of IL-1β and augmented secretion of IL-6, which correlated with decreased airway surface liquid depth as assessed by micro-optical coherence tomography. These findings were paralleled by increased ERK phosphorylation in Fgfr4 -/- airway cells when compared with their control wild-type cells. Analysis of a murine model with constitutive activation of FGFR4 showed attenuation of pro-inflammatory mediators in the lung and airway epithelium. In conclusion, we are the first to show an inflammatory and obstructive airway phenotype in the adult healthy murine Fgfr4 -/- lung, which might be due to the upregulation of ERK phosphorylation in the Fgfr4 -/- airway epithelium.
Related Topics
Concepts
Downregulation and upregulation
Medicine
Fibroblast growth factor receptor 4
Fibroblast growth factor
Lung
MAPK/ERK pathway
Inflammation
COPD
Fibroblast growth factor receptor
Respiratory epithelium
Airway
Cancer research
Immunology
Signal transduction
Biology
Internal medicine
Receptor
Cell biology
Gene
Surgery
Biochemistry
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3389/fmed.2020.00317
- https://www.frontiersin.org/articles/10.3389/fmed.2020.00317/pdf
- OA Status
- gold
- Cited By
- 14
- References
- 36
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3045083974
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W3045083974Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3389/fmed.2020.00317Digital Object Identifier
- Title
-
Fibroblast Growth Factor Receptor 4 Deficiency Mediates Airway Inflammation in the Adult Healthy Lung?Work title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2020Year of publication
- Publication date
-
2020-07-24Full publication date if available
- Authors
-
Molly Easter, Jaleesa M. Garth, Elex S. Harris, Ren‐Jay Shei, E. Scott Helton, Yuhua Wei, Rebecca Denson, Rennan Zaharias, Steven M. Rowe, Patrick Geraghty, Christian Faul, Jarrod W. Barnes, Stefanie KrickList of authors in order
- Landing page
-
https://doi.org/10.3389/fmed.2020.00317Publisher landing page
- PDF URL
-
https://www.frontiersin.org/articles/10.3389/fmed.2020.00317/pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
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https://www.frontiersin.org/articles/10.3389/fmed.2020.00317/pdfDirect OA link when available
- Concepts
-
Downregulation and upregulation, Medicine, Fibroblast growth factor receptor 4, Fibroblast growth factor, Lung, MAPK/ERK pathway, Inflammation, COPD, Fibroblast growth factor receptor, Respiratory epithelium, Airway, Cancer research, Immunology, Signal transduction, Biology, Internal medicine, Receptor, Cell biology, Gene, Surgery, BiochemistryTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
14Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 2, 2024: 6, 2023: 1, 2022: 3, 2021: 2Per-year citation counts (last 5 years)
- References (count)
-
36Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.wanted | 51 |
| abstract_inverted_index.Despite | 96 |
| abstract_inverted_index.chronic | 20 |
| abstract_inverted_index.control | 164 |
| abstract_inverted_index.healthy | 205 |
| abstract_inverted_index.levels, | 101 |
| abstract_inverted_index.mediate | 10 |
| abstract_inverted_index.present | 47 |
| abstract_inverted_index.primary | 117 |
| abstract_inverted_index.results | 68 |
| abstract_inverted_index.spaces, | 83 |
| abstract_inverted_index.surface | 138 |
| abstract_inverted_index.whether | 54 |
| abstract_inverted_index.widened | 81 |
| abstract_inverted_index.<i>)</i> | 31 |
| abstract_inverted_index.Analysis | 167 |
| abstract_inverted_index.assessed | 142 |
| abstract_inverted_index.compared | 161 |
| abstract_inverted_index.disease. | 23 |
| abstract_inverted_index.findings | 148 |
| abstract_inverted_index.indicate | 69 |
| abstract_inverted_index.knockout | 28 |
| abstract_inverted_index.receptor | 3 |
| abstract_inverted_index.reports, | 26 |
| abstract_inverted_index.augmented | 129 |
| abstract_inverted_index.bronchial | 87 |
| abstract_inverted_index.coherence | 145 |
| abstract_inverted_index.decreased | 136 |
| abstract_inverted_index.increased | 84, 124, 152 |
| abstract_inverted_index.mediators | 181 |
| abstract_inverted_index.phenotype | 38, 78, 201 |
| abstract_inverted_index.pulmonary | 22 |
| abstract_inverted_index.secretion | 130 |
| abstract_inverted_index.signaling | 12 |
| abstract_inverted_index.wild-type | 165 |
| abstract_inverted_index.Fibroblast | 0 |
| abstract_inverted_index.Therefore, | 49 |
| abstract_inverted_index.abrogation | 113 |
| abstract_inverted_index.activation | 174 |
| abstract_inverted_index.consistent | 93 |
| abstract_inverted_index.consisting | 79 |
| abstract_inverted_index.correlated | 134 |
| abstract_inverted_index.deficiency | 45 |
| abstract_inverted_index.emphysema. | 95 |
| abstract_inverted_index.epithelium | 18 |
| abstract_inverted_index.expression | 125 |
| abstract_inverted_index.paralleled | 150 |
| abstract_inverted_index.signaling, | 116 |
| abstract_inverted_index.attenuation | 178 |
| abstract_inverted_index.conclusion, | 189 |
| abstract_inverted_index.demonstrate | 75 |
| abstract_inverted_index.epithelium. | 187, 225 |
| abstract_inverted_index.hypertrophy | 92 |
| abstract_inverted_index.interleukin | 102 |
| abstract_inverted_index.obstructive | 21, 199 |
| abstract_inverted_index.tomography. | 146 |
| abstract_inverted_index.ventricular | 91 |
| abstract_inverted_index.<i>Fgfr4</i> | 72, 109, 119, 156, 207, 222 |
| abstract_inverted_index.constitutive | 173 |
| abstract_inverted_index.inflammatory | 197 |
| abstract_inverted_index.obstruction, | 88 |
| abstract_inverted_index.upregulation | 216 |
| abstract_inverted_index.(<i>Fgfr4</i> | 29 |
| abstract_inverted_index.inflammation, | 86 |
| abstract_inverted_index.micro-optical | 144 |
| abstract_inverted_index.<sup>-/-</sup> | 30, 73, 110, 120, 157, 208, 223 |
| abstract_inverted_index.downregulation | 97 |
| abstract_inverted_index.developmentally | 39 |
| abstract_inverted_index.phosphorylation | 154, 219 |
| abstract_inverted_index.simultaneously. | 48 |
| abstract_inverted_index.pro-inflammatory | 11, 180 |
| cited_by_percentile_year.max | 98 |
| cited_by_percentile_year.min | 89 |
| corresponding_author_ids | https://openalex.org/A5020903748 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 13 |
| corresponding_institution_ids | https://openalex.org/I32389192 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.8199999928474426 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.64702931 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |