Hepatocyte Growth Factor Delivered by Nanocomposites for Gene Therapy of Bleomycin-Induced Pulmonary Fibrosis in Rats

Abstract

Background: Pulmonary fibrosis (PF) is a chronic and progressive interstitial lung disease. There is no effective treatment for PF. Hepatocyte growth factor (HGF) has anti-inflammatory and anti-fibrotic effects, but has limited potential owing to its short half-life. Methods: To increase the transfection efficiency of pVAX-HGF, we prepared polyethyleneimine-polyethylene glycol: polyethyleneimine/pVAX-HGF (PEG-PEI: PEI/pVAX-HGF) nanocomposite loaded with a plasmid encoding the HGF gene. The PEG-PEI:PEI/pVAX-HGF characteristics, including morphology, particle size, zeta-potential, and DNA entrapment efficiency, were investigated. The pVAX-HGF nanocomposites with low toxicity and high transfection efficiency were screened by cell viability assay and cell transfection. The antifibrotic effect of pVAX-HGF nanocomposite on PF rats induced by bleomycin (BLM) was evaluated by pulmonary function measurement, pathological examination and collagen content assay. Results: Different nanocomposites were prepared to deliver pVAX-HGF, in which mix1 (PEG-PEI:PEI/pVAX-HGF) has lower potential and better entrapment ability. And PEG-PEI:PEI/pVAX-HGF (N/P=25) nanocomposite with low toxicity and high transfection efficiency was administered to PF rats. After treatment with mix 1/pVAX-HGF, the index of lung function(including EF50, MV, TV, PEF and PIF) in mix 1/pVAX-HGF group was higher that of PF group. The number of cells in BALF of the mix 1/pVAX-HGF group was significantly lower than that of the PF groups, and the content of hydroxyproline(HYP) and collagen Type I (Col-I) in the lung of the mix 1/pVAX-HGF group was much lower than that of the PF groups in the early stage. The result of pathological examination showed that rats in the mix1/pVAX-HGF group showed obviously reduced alveolar septal thickening, fewer infiltrated inflammatory cells and less collagen deposition. Conclusion: The PEG-PEI:PEI/pVAX-HGF nanocomposite can ameliorate PF induced by BLM. The pVAX-HGF nanocomposite is a latent therapeutic strategy for PF.

Microvesicles derived from mesenchymal stem cells inhibit ARDS pulmonary fibrosis partly through HGF

“…The HGF is a cell repair factor that promotes epithelial cell proliferation, collagen degradation, and inhibits epithelial cell apoptosis. It is one of the few growth factors that can inhibit brosis [31][32][33]. The MSC-MVs contain abundant mRNA, such as HGF mRNA [34]; RNA transfer is an important way by which MSC-MVs exert damage repair effects [35][36].…”