title: Hepatocyte growth factor gene-modified mesenchymal stem cells reduce radiation-induced lung injury.
abstract: Abstract Effective therapeutic strategies for radiation-induced lung injury (RILI) are lacking. Mesenchymal stem cells (MSCs), as gene therapy delivery vehicles, possess the ability to repair injured lung. In this study, we conducted MSC-based hepatocyte growth factor (HGF) gene therapy for RILI. Mice received single-dose radiation with 20 Gy of γ rays locally to the lung, and then were administered normal sodium, Ad-HGF-modified MSCs, or Ad-Null-modified MSCs. Ad-HGF-modified MSCs (MSCs-HGF) improved histopathological and biochemical markers of lung injury. MSCs-HGF could reduce secretion and expression of proinflammatory cytokines, including tumor necrosis factor-α, interferon-γ, interleukin (IL)-6, and intercellular adhesion molecule-1, and increase the expression of antiinflammatory cytokine IL-10. It could also decrease expression levels of profibrosis factors transforming growth factor-β, Col1a1 (collagen type 1, α1), and Col3a1, and inhibit fibrosis progress. MSCs-HGF could promote proliferation of lung epithelial cells and protect them from apoptosis, and improve the expression of endogenous HGF and its receptor c-Met significantly. We also found that sphingosine-1-phosphate receptor-1 expression was increased in injured lung. These results suggest MSC-based HGF gene therapy not only reduces inflammation but also inhibits lung fibrosis.
authors: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, People's Republic of China .
authors: Hua
authors: H
authors: Wang
authors: Yue-Feng
authors: YF
authors: Yang
authors: Li
authors: L
authors: Zhao
authors: Feng-Jun
authors: FJ
authors: Xiao
authors: Qun-Wei
authors: QW
authors: Zhang
authors: Ming-Ling
authors: ML
authors: Wen
authors: Chu-Tse
authors: CT
authors: Wu
authors: Rui-Yun
authors: RY
authors: Peng
authors: Li-Sheng
authors: LS
authors: Wang
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D056809:Alveolar Epithelial Cells / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D017228:Hepatocyte Growth Factor / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D055370:Lung Injury / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D010539:Permeability; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D049349:Receptors, Lysosphingolipid / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D049349:Receptors, Lysosphingolipid; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met