title: Wnt/β-catenin signaling induces the aging of mesenchymal stem cells through promoting the ROS production.
abstract: Recent studies have demonstrated that the Wnt/β-catenin signaling plays an important role in stem cell aging. However, the mechanisms of cell senescence induced by Wnt/β-catenin signaling are still poorly understood. Our preliminary study has indicated that activated Wnt/β-catenin signaling can induce MSC aging. In this study, we reported that the Wnt/β-catenin signaling was a potent activator of reactive oxygen species (ROS) generation in MSCs. After scavenging ROS with N-acetylcysteine, Wnt/β-catenin signaling-induced MSC aging was significantly attenuated and the DNA damage and the expression of p16(INK4A), p53, and p21 were reduced in MSCs. These results indicated that the Wnt/β-catenin signaling could induce MSC aging through promoting the intracellular production of ROS, and ROS may be the main mediators of MSC aging induced by excessive activation of Wnt/β-catenin signaling.
authors.affiliation: Department of Basic Medicine, School of Medicine and Life Sciences, Zhejiang University City College, 51 Huzhou Street, Hangzhou, 310015, People's Republic of China.
authors.forename: Da-Yong
authors.initials: DY
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Pan
authors.forename: Chong
authors.initials: C
authors.lastname: Zhang
authors.forename: Bing-Xi
authors.initials: BX
authors.lastname: Yan
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Yu
authors.forename: Dong-Ling
authors.initials: DL
authors.lastname: Wu
authors.forename: Meng-Meng
authors.initials: MM
authors.lastname: Shi
authors.forename: Kai
authors.initials: K
authors.lastname: Shi
authors.forename: Xin-Xiao
authors.initials: XX
authors.lastname: Cai
authors.forename: Shuang-Shuang
authors.initials: SS
authors.lastname: Zhou
authors.forename: Jun-Bo
authors.initials: JB
authors.lastname: Wang
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Pan
authors.forename: Li-Huang
authors.initials: LH
authors.lastname: Zhang
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D016922:Cellular Senescence; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis; D004249:DNA Damage / Q000187:drug effects; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D034622:RNA Interference; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C493958:Cdkn1a protein, rat; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D051153:Wnt Proteins; D051176:beta Catenin; D000111:Acetylcysteine