Fytianos, Kleanthis; Schliep, Ronja; Mykoniati, Sofia; Khan, Petra; Hostettler, Katrin E; Tamm, Michael; Gazdhar, Amiq; Knudsen, Lars; Geiser, Thomas (2022). Anti-Fibrotic Effect of SDF-1β Overexpression in Bleomycin-Injured Rat Lung. Pharmaceutics, 14(9) MDPI 10.3390/pharmaceutics14091803
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Rational: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease and is associated with high mortality due to a lack of effective treatment. Excessive deposition of the extracellular matrix by activated myofibroblasts in the alveolar space leads to scar formation that hinders gas exchange. Therefore, selectively removing activated myofibroblasts with the aim to repair and remodel fibrotic lungs is a promising approach. Stromal-derived growth factor (SDF-1) is known to stimulate cellular signals which attract stem cells to the site of injury for tissue repair and remodeling. Here, we investigate the effect of overexpression of SDF-1β on lung structure using the bleomycin-injured rat lung model. Methods: Intratracheal administration of bleomycin was performed in adult male rats (F344). Seven days later, in vivo electroporation-mediated gene transfer of either SDF-1β or the empty vector was performed. Animals were sacrificed seven days after gene transfer and histology, design-based stereology, flow cytometry, and collagen measurement were performed on the tissue collected. For in vitro experiments, lung fibroblasts obtained from IPF patients were used. Results: Seven days after SDF-1β gene transfer to bleomycin-injured rat lungs, reduced total collagen, reduced collagen fibrils, improved histology and induced apoptosis of myofibroblasts were observed. Furthermore, it was revealed that TNF-α mediates SDF-1β-induced apoptosis of myofibroblasts; moreover, SDF-1β overexpression increased alveolar epithelial cell numbers and proliferation in vivo and also induced their migration in vitro. Conclusions: Our study demonstrates a new antifibrotic mechanism of SDF-1β overexpression and suggests SDF-1β as a potential new approach for the treatment of lung fibrosis.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Pneumologie (Erwachsene) 04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Pneumology |
UniBE Contributor: |
Fytianos, Kleanthis, Gazdhar, Amiq, Geiser, Thomas (A) |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1999-4923 |
Publisher: |
MDPI |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
27 Sep 2022 09:26 |
Last Modified: |
29 Mar 2023 23:38 |
Publisher DOI: |
10.3390/pharmaceutics14091803 |
PubMed ID: |
36145551 |
Uncontrolled Keywords: |
IPF SDF-1b alveolar epithelial cell proliferation interstitial lung disease lung fibrosis lung repair and regeneration myofibroblast apoptosis nonviral gene therapy |
BORIS DOI: |
10.48350/173231 |
URI: |
https://boris.unibe.ch/id/eprint/173231 |
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