title: Bone marrow mesenchymal stem cells protect alveolar macrophages from lipopolysaccharide-induced apoptosis partially by inhibiting the Wnt/β-catenin pathway.
abstract: Apoptosis of alveolar macrophages (AMs) plays a pathogenic role in acute lung injury (ALI) and its severe type, acute respiratory distress syndrome (ARDS). Mesenchymal stem cells (MSCs) are promising therapeutic cells for preventing apoptosis and eliminating cellular injury. We investigated the effects of rat bone marrow mesenchymal stem cells (BMSCs) on lipopolysaccharide (LPS)-induced apoptosis in AMs using transwell experiments, and examined the underlying mechanisms LPS induced AMs apoptosis in a dose- and time-dependent fashion, whereas BMSCs reduced AMs apoptosis when co-cultured at appropriate ratios. BMSCs decreased expression of cleaved caspase-3 and the pro-apoptotic protein, Bax, whilst increased levels of the anti-apoptotic protein, Bcl-2, prolonging the lifespan of AMs in vitro. Promotion of AMs survival by BMSCs required down-regulation of p-GSK-3β and β-catenin in AMs. The anti-apoptosis action of BMSCs was reversed by SB216763, a specific inhibitor of GSK-3β that also activates Wnt/β-catenin signaling. In conclusion, BMSCs can attenuate AM apoptosis partially by suppressing the Wnt/β-catenin pathway.
authors.affiliation: Department of MICU, The First Affiliated Hospital, Sun Yat-Sen University, 58# Zhongshan 2nd Road, Guangzhou, 510080, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Hongwu
authors.initials: H
authors.lastname: Zhang
authors.forename: Mian
authors.initials: M
authors.lastname: Zeng
authors.forename: Wanmei
authors.initials: W
authors.lastname: He
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: Xubin
authors.initials: X
authors.lastname: Huang
authors.forename: David Y B
authors.initials: DY
authors.lastname: Deng
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Wu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001854:Bone Marrow Cells / Q000166:cytology*; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D016130:Immunophenotyping; D007211:Indoles / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity*; D016676:Macrophages, Alveolar / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008301:Maleimides / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D018613:Microscopy, Confocal; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D007211:Indoles; D008070:Lipopolysaccharides; D008301:Maleimides; D019253:Proto-Oncogene Proteins c-bcl-2; C417521:SB 216763; D051153:Wnt Proteins; D051028:bcl-2-Associated X Protein; D051176:beta Catenin; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; D053148:Caspase 3
keywords: ALI/ARDS; Wnt/β-catenin pathway; alveolar macrophage; apoptosis; bone marrow mesenchymal cells; sepsis