title: Mesenchymal stem cells protects hyperoxia-induced lung injury in newborn rats via inhibiting receptor for advanced glycation end-products/nuclear factor κB signaling.
abstract: Bone marrow-derived mesenchymal stem cells (BMSCs) have been shown recently to ameliorate hyperoxia-induced lung injury, but the underlying mechanism remains unclear. This study aimed to determine whether BMSCs attenuate hyperoxia-induced lung injury by down-modulating the inflammatory RAGE/NF-κB (receptor for advanced glycation end-products/nuclear factor-κB) signaling. Thirty Sprague-Dawley newborn rats were randomly divided into three groups (n = 10): sham control (C); hyperoxia-induced acute lung injury (ALI) (B) and ALI with BMSCs transplantation (A). Rats were sacrificed at three-day post-transplantation. RAGE and NF-κB expression in lung tissue was detected by reverse transcription polymerase chain reaction, Western blot and immunohistochemistry analysis. The levels of tumor necrosis factor α (TNF-α) and RAGE in bronchoalveolar lavage fluid (BALF) and in serum were detected by enzyme-linked immunosorbent assay. The lung damage was evaluated by histological examination. The results showed that RAGE and TNF-α concentrations in BALF were significantly lower in Group A than in Group B. Moreover, RAGE and NF-κB expression in lung tissue at mRNA and protein concentrations was significantly lower in Group A than in Group B. The lung damage score was significantly lower in Group A than in Group B. These data demonstrate that hyperoxia induces the inflammation and causes damage in the lung but BMSC transplantation could alleviate hyperoxia-induced lung injury by inhibiting the inflammatory process mediated by RAGE/NF-κB signaling.
authors.affiliation: Department of Neonatology, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, Jiangsu 223300, PR China. tianzhaofan@163.com
authors.forename: Zhaofang
authors.initials: Z
authors.lastname: Tian
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Li
authors.forename: Ping
authors.initials: P
authors.lastname: Ji
authors.forename: Sai
authors.initials: S
authors.lastname: Zhao
authors.forename: Huaipin
authors.initials: H
authors.lastname: Cheng
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors*; D006651:Histocytochemistry; D018496:Hyperoxia / Q000150:complications*; D007150:Immunohistochemistry; D008168:Lung / Q000473:pathology; D055370:Lung Injury / Q000139:chemically induced / Q000517:prevention & control*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D017127:Glycation End Products, Advanced; D016328:NF-kappa B; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha