Work

490. Electroporation-Mediated Gene Transfer of Caveolin-1 Protects from Bleomycin-Induced Pulmonary Fibrosis Through Regulating Activation of Inflammasome

Year: 2016

Type: article

Abstract: Pulmonary fibrosis (PF) is a progressive chronic interstitial lung disease associated with high morbidity and mortality. It is characterized by increased deposition of extracellular matrix proteins and the accumulation of scar tissue in the lung interstitium, resulting from alveolar epithelial injury and the accumulation of inflammatory cells. Currently, there is no effective therapy. Gene therapy is a promising approach to treat a variety of lung diseases, including pulmonary fibrosis. Caveolin-1 (Cav-1) is a major component of caveolae, and has been found greatly reduced expression in the lungs of PF patients. Moreover, Cav-1-deficient mice develop spontaneous pulmonary fibrosis. To investigate if Cav-1 can protect from bleomycin-induced pulmonary fibrosis, we delivered plasmids expressing Cav-1 driven by the ubiquitin promoter using electroporation. PF was induced 2 days after gene transfer by intratracheal administration of bleomycin (2 unit/kg). We found that electroporation-mediated gene transfer of Cav-1 to the lung significantly protected from subsequent bleomycin-mediated fibrogenesis by histological analysis and the expression of alpha-smooth muscle actin (alpha-SMA) and collagen measurement. We also found attenuated recruitment of neutrophils and monocytes and/or macrophages in bronchoalveolar lavage (BAL) fluid after gene transfer of Cav-1 compared with vector control. The underlying mechanism was associated with reduced activation of the inflammasome by determining the expression of cleaved caspase-1 and IL-1 beta in both mouse models and cultured cells after overexpression of Cav-1. These results demonstrate that Cav-1 might be a potential target for treatment of pulmonary fibrosis.

Source: Molecular Therapy

DOI: 10.1016/s1525-0016(16)33299-3

Authors: Xin Lin, Michael Barravecchia, David A Dean

Institutions: University of Rochester Medicine, University of Rochester

Language: English

Topic: Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,500