2. Academic Validation
  3. Anti-Fibrotic Effect of SDF-1β Overexpression in Bleomycin-Injured Rat Lung

Anti-Fibrotic Effect of SDF-1β Overexpression in Bleomycin-Injured Rat Lung

  • Pharmaceutics. 2022 Aug 27;14(9):1803. doi: 10.3390/pharmaceutics14091803.
Kleanthis Fytianos 1 2,  Ronja Schliep 3,  Sofia Mykoniati 4,  Petra Khan 5,  Katrin E Hostettler 5,  Michael Tamm 5,  Amiq Gazdhar 1 2,  Lars Knudsen 3,  Thomas Geiser 1 2
Affiliations

Affiliations

  • 1 Department of Pulmonary Medicine, University Hospital Bern, 3010 Bern, Switzerland.
  • 2 Department of Biomedical research, University of Bern, 3010 Bern, Switzerland.
  • 3 Institute of Functional and Applied Anatomy, Hannover Medical School, 30625 Hanover, Germany.
  • 4 Department of Internal Medicine, Cantonal Hospital of Jura, 2800 Delemont, Switzerland.
  • 5 Department of Biomedical Research and Clinics of Respiratory Medicine, University Hospital Basel, University of Basel, 4031 Basel, Switzerland.
PMID: 36145551 DOI: 10.3390/pharmaceutics14091803
Abstract

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.

Keywords

IPF; SDF-1b; alveolar epithelial cell proliferation; interstitial lung disease; lung fibrosis; lung repair and regeneration; myofibroblast apoptosis; nonviral gene therapy.

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