title: Keratinocyte growth factor gene delivery via mesenchymal stem cells protects against lipopolysaccharide-induced acute lung injury in mice.
abstract: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are associated with high morbidity and mortality, and have no specific therapy. Keratinocyte growth factor (KGF) is a critical factor for pulmonary epithelial repair and acts via the stimulation of epithelial cell proliferation. Mesenchymal stem cells (MSCs) have been proved as good therapeutic vectors. Thus, we hypothesized that MSC-based KGF gene therapy would have beneficial effects on lipopolysaccharide(LPS)-induced lung injury. After two hours of intratracheal LPS administration to induce lung injury, mice received saline, MSCs alone, empty vector-engineered MSCs (MSCs-vec) or KGF-engineered MSCs (MSCs-kgf) via the tail vein. The MSCs-kgf could be detected in the recipient lungs and the level of KGF expression significantly increased in the MSCs-kgf mice. The MSC-mediated administration of KGF not only improved pulmonary microvascular permeability but also mediated a down-regulation of proinflammatory responses (reducing IL-1β and TNF-α) and an up-regulation of anti-inflammatory responses (increasing cytokine IL-10). Furthermore, the total severity scores of lung injury were significantly reduced in the MSCs-kgf group compared with the other three groups. The underlying mechanism of the protective effect of KGF on ALI may be attributed to the promotion of type II lung epithelial cell proliferation and the enhancement of surfactant synthesis. These findings suggest that MSCs-based KGF gene therapy may be a promising strategy for ALI treatment.
authors.affiliation: Department of Respiratory Medicine, Chinese People's Liberation Army General Hospital, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Respiratory Medicine, Chinese People's Liberation Army General Hospital, Beijing, China.
authors.forename: Chunsun
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, Chinese People's Liberation Army General Hospital, Beijing, China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Respiratory Medicine, Chinese People's Liberation Army General Hospital, Beijing, China.
authors.forename: Chonghui
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, Chinese People's Liberation Army General Hospital, Beijing, China.
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Department of Respiratory Medicine, Chinese People's Liberation Army General Hospital, Beijing, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Respiratory Medicine, Chinese People's Liberation Army General Hospital, Beijing, China.
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, Chinese People's Liberation Army General Hospital, Beijing, China.
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Respiratory Medicine, Chinese People's Liberation Army General Hospital, Beijing, China.
authors.forename: Liangan
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D019610:Cytoprotection; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D051523:Fibroblast Growth Factor 7 / Q000235:genetics*; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000473:pathology; D055370:Lung Injury / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D051379:Mice; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D014161:Transduction, Genetic
chemical_list: D008070:Lipopolysaccharides; D008565:Membrane Proteins; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D051523:Fibroblast Growth Factor 7