The pathogenic role of smooth muscle cell-derived Wnt5a in a murine model of lung fibrosis
- Idiopathic pulmonary fibrosis (IPF) is a disease characterized by extensive fibrosis of the lung tissue. Wnt5a expression was observed to be upregulated in IPF and suggested to be involved in the progression of the disease. Interestingly, smooth muscle cells (SMC) are a major source of Wnt5a in IPF patients. However, no study has been conducted until now to investigate the precise role of smooth muscle-derived Wnt5a in IPF. Here, we used the bleomycin-induced lung fibrosis model in a conditional gene-deficient mouse, where the Wnt5a gene was excised from SMC. We show here that the excision of the Wnt5a gene in SMC led to significantly improved health conditions with minimized weight loss and improved lung function. This improvement was based on a significantly lower deposition of collagen in the lung with a reduced number of fibrotic foci in lung parenchyma. Furthermore, the bleomycin-induced cellular infiltration into the airways was not altered in the gene-deficient mice compared with wild-type mice. Thus, we demonstrate that the Wnt5a expression of SMC of the airways leads to aggravated fibrosis of the lung with poor clinical conditions. This aggravation was not an influence in the bleomycin-induced inflammatory processes but on the development of fibrotic foci in lung parenchyma and the deposition of collagen.
Author: | André Carmo-FernandesORCiDGND, Michelle PuschkarowGND, Karin PetersGND, Stefanie GnippGND, Marcus PetersORCiDGND |
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URN: | urn:nbn:de:hbz:294-88039 |
DOI: | https://doi.org/10.3390/ph14080755 |
Parent Title (English): | Pharmaceuticals |
Publisher: | MDPI |
Place of publication: | Basel |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2022/03/31 |
Date of first Publication: | 2021/07/31 |
Publishing Institution: | Ruhr-Universität Bochum, Universitätsbibliothek |
Tag: | Open Access Fonds Wingless-Type MMTV integration site family; airway smooth muscle; bleomycin; fibrotic foci; member 5A; pulmonary fibrosis |
Volume: | 14 |
Issue: | 8, Artikel 755 |
First Page: | 755-1 |
Last Page: | 755-13 |
Note: | Article Processing Charge funded by the Open Access Publication Fund of Ruhr-Universität Bochum. |
Institutes/Facilities: | Abteilung für Experimentelle Pneumologie |
Lehrstuhl für Molekulare Immunologie | |
Dewey Decimal Classification: | Technik, Medizin, angewandte Wissenschaften / Medizin, Gesundheit |
open_access (DINI-Set): | open_access |
Licence (English): | Creative Commons - CC BY 4.0 - Attribution 4.0 International |