title: Activation of canonical wnt pathway promotes differentiation of mouse bone marrow-derived MSCs into type II alveolar epithelial cells, confers resistance to oxidative stress, and promotes their migration to injured lung tissue in vitro.
abstract: The differentiation of mesenchymal stem cells (MSCs) into type II alveolar epithelial (AT II) cells in vivo and in vitro, is critical for reepithelization and recovery in acute lung injury (ALI), but the mechanisms responsible for differentiation are unclear. In the present study, we investigated the role of the canonical wnt pathway in the differentiation of mouse bone marrow-derived MSCs (mMSCs) into AT II cells. Using a modified co-culture system with murine lung epithelial-12 (MLE-12) cells and small airway growth media (SAGM) to efficiently drive mMSCs differentiation, we found that GSK 3β and β-catenin in the canonical wnt pathway were up-regulated during differentiation. The levels of surfactant protein (SP) C, SPB, and SPD, the specific markers of AT II cells, correspondingly increased in mMSCs when Wnt3a or LiCl was added to the co-culture system to activate wnt/β-catenin signaling. The expression of these factors was depressed to some extent by inhibiting the pathway with the addition of DKK 1. The differentiation rate of mMSCs also depends on their abilities to accumulate and survive in inflammatory tissue. Our results suggested that the activation of wnt/β-catenin signaling promoted mMSCs migration towards ALI mouse-derived lung tissue in a Transwell assay, and ameliorated the cell death and the reduction of Bcl-2/Bax induced by H(2) O(2), which simultaneously caused reduced GSK 3β and β-catenin in mMSCs. These data supports a potential mechanism for the differentiation of mMSCs into AT II cells involving canonical wnt pathway activation, which may be significant to their application in ALI.
authors.affiliation: Department of Critical Care Medicine, Zhong-da Hospital, School of Medicine, Southeast University, Nanjing, P.R. China.
authors.forename: Ai-Ran
authors.initials: AR
authors.lastname: Liu
authors.forename: Le
authors.initials: L
authors.lastname: Liu
authors.forename: Song
authors.initials: S
authors.lastname: Chen
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Hong-Jie
authors.initials: HJ
authors.lastname: Zhao
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.forename: Feng-Mei
authors.initials: FM
authors.lastname: Guo
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Lu
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Qiu
mesh_terms: D055371:Acute Lung Injury / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D056809:Alveolar Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000637:transplantation; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006861:Hydrogen Peroxide / Q000494:pharmacology; D018021:Lithium Chloride / Q000494:pharmacology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D062326:Re-Epithelialization; D013997:Time Factors; D046509:Tissue Culture Techniques; D060449:Wnt Signaling Pathway / Q000187:drug effects; D060509:Wnt3A Protein / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015415:Biomarkers; C495267:CTNNB1 protein, mouse; D017077:Culture Media, Conditioned; D016877:Oxidants; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; D051176:beta Catenin; D006861:Hydrogen Peroxide; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride