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Fibroblast growth factor 10 reverses cigarette smoke- and elastase-induced emphysema and pulmonary hypertension in mice.
- Source :
-
The European respiratory journal [Eur Respir J] 2023 Nov 09; Vol. 62 (5). Date of Electronic Publication: 2023 Nov 09 (Print Publication: 2023). - Publication Year :
- 2023
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Abstract
- Background: COPD is an incurable disease and a leading cause of death worldwide. In mice, fibroblast growth factor (FGF)10 is essential for lung morphogenesis, and in humans, polymorphisms in the human FGF10 gene correlate with an increased susceptibility to develop COPD.<br />Methods: We analysed FGF10 signalling in human lung sections and isolated cells from healthy donor, smoker and COPD lungs. The development of emphysema and PH was investigated in Fgf10 <superscript>+/-</superscript> and Fgfr2b <superscript>+/-</superscript> (FGF receptor 2b) mice upon chronic exposure to cigarette smoke. In addition, we overexpressed FGF10 in mice following elastase- or cigarette smoke-induced emphysema and pulmonary hypertension (PH).<br />Results: We found impaired FGF10 expression in human lung alveolar walls and in primary interstitial COPD lung fibroblasts. In contrast, FGF10 expression was increased in large pulmonary vessels in COPD lungs. Consequently, we identified impaired FGF10 signalling in alveolar walls as an integral part of the pathomechanism that leads to emphysema and PH development: mice with impaired FGF10 signalling ( Fgf10 <superscript>+/-</superscript> and Fgfr2b <superscript>+/-</superscript> ) spontaneously developed lung emphysema, PH and other typical pathomechanistic features that generally arise in response to cigarette smoke exposure.<br />Conclusion: In a therapeutic approach, FGF10 overexpression successfully restored lung alveolar and vascular structure in mice with established cigarette smoke- and elastase-induced emphysema and PH. FGF10 treatment triggered an initial increase in the number of alveolar type 2 cells that gradually returned to the basal level when the FGF10-mediated repair process progressed. Therefore, the application of recombinant FGF10 or stimulation of the downstream signalling cascade might represent a novel therapeutic strategy in the future.<br />Competing Interests: Conflict of interest: The authors have no potential conflicts of interest to disclose.<br /> (Copyright ©The authors 2023.)
- Subjects :
- Humans
Animals
Mice
Pancreatic Elastase adverse effects
Pancreatic Elastase metabolism
Fibroblast Growth Factor 10 metabolism
Fibroblast Growth Factor 10 therapeutic use
Receptor, Fibroblast Growth Factor, Type 2 genetics
Receptor, Fibroblast Growth Factor, Type 2 metabolism
Receptor, Fibroblast Growth Factor, Type 2 therapeutic use
Lung metabolism
Mice, Inbred C57BL
Pulmonary Disease, Chronic Obstructive drug therapy
Hypertension, Pulmonary complications
Cigarette Smoking adverse effects
Pulmonary Emphysema etiology
Emphysema complications
Subjects
Details
- Language :
- English
- ISSN :
- 1399-3003
- Volume :
- 62
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- The European respiratory journal
- Publication Type :
- Academic Journal
- Accession number :
- 37884305
- Full Text :
- https://doi.org/10.1183/13993003.01606-2022