title: Protection against hyperoxia-induced lung fibrosis by KGF-induced MSCs mobilization in neonatal rats.
abstract: MSCs have been shown to improve functional and pathological outcome in lung fibrosis. However, low in vivo cell engraftment of the transplanted cells limits their overall effectiveness. KGF (also known as FGF-7) is a critical mediator of pulmonary epithelial repair through stimulation of epithelial cell proliferation. However, the role of KGF in MSCs and its therapeutic effects have not been identified. In this study, we investigated the effect of KGF on MSCs and its preventive role in hyperoxia-induced fibrosis in neonatal rats. Neonatal rats exposed to normoxia or hyperoxia were randomly assigned to receive intraperitoneal injections of normal saline (PL), MSCs, or KGF pretreated MSCs on the fourth day of exposure. Our results showed that as compared to PL, while MSCs attenuated lung fibrosis, KGF pretreated MSCs exhibited enhanced preventive effect against lung fibrosis. This effect was partly attributed to enhanced mobilization of MSCs to the fibrotic lungs. In addition, the SHH signaling pathway, which is associated with the differentiation of stem cells was activated by KGF. Our data suggest that MSCs, especially KGF preconditioned MSCs, can attenuate lung fibrosis and KGF may regulate the MSCs behavior by activating SHH pathway.
authors.affiliation: Department of Intensive Care Unit, Children's Hospital of Chongqing Medical University, Chongqing, China; Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Center for Child Development and Disorders, Chongqing Medical University, Chongqing, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Yao
authors.forename: Cheng-jun
authors.initials: CJ
authors.lastname: Liu
authors.forename: Qing
authors.initials: Q
authors.lastname: Luo
authors.forename: Min
authors.initials: M
authors.lastname: Gong
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Li-Jia
authors.initials: LJ
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Jiang
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.forename: Ting-Yu
authors.initials: TY
authors.lastname: Li
authors.forename: Chang
authors.initials: C
authors.lastname: Shu
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D017690:Cell Transplantation / Q000379:methods*; D005260:Female; D051523:Fibroblast Growth Factor 7 / Q000378:metabolism*; D005355:Fibrosis; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D053823:Hedgehog Proteins / Q000378:metabolism; D006909:Hydroxyproline / Q000737:chemistry; D018496:Hyperoxia / Q000378:metabolism / Q000473:pathology*; D008168:Lung / Q000473:pathology; D055370:Lung Injury / Q000473:pathology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology; D015854:Up-Regulation
chemical_list: C496455:Fgf7 protein, rat; D053823:Hedgehog Proteins; C546888:Shh protein, rat; D051523:Fibroblast Growth Factor 7; C496356:Fgfr2 protein, rat; D051497:Receptor, Fibroblast Growth Factor, Type 2; D006909:Hydroxyproline
keywords: KGF; MSC; SHH; hyperoxia; lung fibrosis