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Hepatocyte Growth Factor Gene Transfer to Alveolar Septa for Effective Suppression of Lung Fibrosis
- Source :
- Molecular Therapy. 12(1):58-67
- Publication Year :
- 2005
- Publisher :
- Elsevier BV, 2005.
-
Abstract
- We examined therapeutic gene transfer of human hepatocyte growth factor (hHGF) to alveolar septa in mouse bleomycin-induced lung fibrosis using macroaggregated albumin-polyethylenimine complex (MAA-PEI). Intravenous administration of MAA-PEI along with 1 μg pCAG.hHGF to C57BL/6 mice increased the uptake of plasmids into alveolar capillary endothelial cells and epithelial cells, prolonged hHGF expression in the lung, and induced a level of hHGF expression equal to that seen with 10 μg of hHGF-expression plasmids alone. The exogenous source of hHGF gene expression increased the endogenous mouse HGF in the lungs and significantly decreased TNF-α, IL-6, and collagen synthesis after bleomycin injury. Because GFP-labeled bone marrow-derived stem cells after bleomycin injury were reduced in number by HGF, the primary mechanism of HGF is likely to be the prevention of apoptosis, as has been suggested by in vitro experiments. This novel HGF gene transfer method to alveolar septa with nonstimulatory MAA-PEI conjugates may have promising clinical applications.
- Subjects :
- medicine.medical_treatment
Genetic enhancement
Pulmonary Fibrosis
Genetic Vectors
Apoptosis
Bone Marrow Cells
Biology
Bleomycin
chemistry.chemical_compound
Mice
Albumins
Pulmonary fibrosis
Gene expression
Drug Discovery
medicine
Genetics
Animals
Polyethyleneimine
Molecular Biology
Pharmacology
Lung
Hepatocyte Growth Factor
Growth factor
Stem Cells
Technetium
Genetic Therapy
respiratory system
medicine.disease
Pulmonary Alveoli
medicine.anatomical_structure
chemistry
Immunology
Cancer research
Cytokines
Molecular Medicine
Hepatocyte growth factor
Stem cell
medicine.drug
Subjects
Details
- ISSN :
- 15250016
- Volume :
- 12
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Molecular Therapy
- Accession number :
- edsair.doi.dedup.....c737f38bfdb2ce83beecbd9e2c048c38
- Full Text :
- https://doi.org/10.1016/j.ymthe.2005.02.019