title: Wnt5a through noncanonical Wnt/JNK or Wnt/PKC signaling contributes to the differentiation of mesenchymal stem cells into type II alveolar epithelial cells in vitro.
abstract: The differentiation of mesenchymal stem cells (MSCs) into type II alveolar epithelial (AT II) cells is critical for reepithelization and recovery in acute respiratory distress syndrome (ARDS), and Wnt signaling was considered to be the underlying mechanisms. In our previous study, we found that canonical Wnt pathway promoted the differentiation of MSCs into AT II cells, however the role of the noncanonical Wnt pathway in this process is unclear. It was disclosed in this study that noncanonical Wnt signaling in mouse bone marrow-derived MSCs (mMSCs) was activated during the differentiation of mMSCs into AT II cells in a modified co-culture system with murine lung epithelial-12 cells and small airway growth media. The levels of surfactant protein (SP) C, SPB and SPD, the specific markers of AT II cells, increased in mMSCs when Wnt5a was added to activate noncanonical Wnt signaling, while pretreatment with JNK or PKC inhibitors reversed the promotion of Wnt5a. The differentiation rate of mMSCs also depends on their abilities to accumulate and survive in inflammatory tissue. We found that the Wnt5a supplement promoted the vertical and horizontal migration of mMSCs, ameliorated the cell death and the reduction of Bcl-2/Bax induced by H2O2. The effect of Wnt5a on the migration of mMSCs and their survival after H2O2 exposure were partially inhibited with PKC or JNK blockers. In conclusion, Wnt5a through Wnt/JNK signaling alone or both Wnt/JNK and Wnt/PKC signaling promoted the differentiation of mMSCs into AT II cells and the migration of mMSCs; through Wnt/PKC signaling, Wnt5a increased the survival of mMSCs after H2O2 exposure in vitro.
authors.affiliation: Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, P. R. China.
authors.forename: Airan
authors.initials: A
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing, P. R. China.
authors.forename: Song
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, P. R. China.
authors.forename: Shixia
authors.initials: S
authors.lastname: Cai
authors.affiliation: Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, P. R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Dong
authors.affiliation: Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, P. R. China.
authors.forename: Le
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, P. R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, P. R. China.
authors.forename: Fengmei
authors.initials: F
authors.lastname: Guo
authors.affiliation: Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, P. R. China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, P. R. China.
authors.forename: Hongli
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, P. R. China.
authors.forename: Qihong
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, P. R. China.
authors.forename: Shuling
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, P. R. China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Qiu
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D018920:Coculture Techniques; D004847:Epithelial Cells; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018384:Oxidative Stress; D011650:Pulmonary Alveoli / Q000166:cytology*; D051153:Wnt Proteins / Q000378:metabolism / Q000502:physiology*; D060449:Wnt Signaling Pathway; D000071818:Wnt-5a Protein
chemical_list: D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse