title: TGF-β1 induces senescence of bone marrow mesenchymal stem cells via increase of mitochondrial ROS production.
abstract: BACKGROUND
  Bone marrow derived mesenchymal stem cells (bmMSCs) are multipotent cells that can differentiate into diverse cell types, including cardiomyocytes. BmMSC-based transplantation is capable of repairing acute and chronic myocardial infarction. Prior to the transplantation, MSCs are usually induced in vitro by biological reagents and chemicals for directional differentiation. Transforming growth factor beta (TGF-β) is one of the most commonly used biological reagents for induction of cardiomyocyte differentiation of bmMSCs. Previous studies have shown that TGF-β induces senescence in several cell types. However, whether TGF-β affects senescence of bmMSCs has not been elucidated. The goal of this study was to investigate the effect of TGF-β1 on senescence of bmMSCs and the underlying mechanisms.
  
  
  RESULTS
  We found that TGF-β1 increased activity of senescence-associated-galactosidase (SA-Gal) and production of mitochondrial reactive oxygen species (mtROS) in bmMSCs in a dose-dependent manner. TGF-β1 also significantly decreased expression of superoxide dismutase 2 (SOD2) and Id1, and increased expression of 4-Hydroxynonenal (4-HNE) subunits and p16 in bmMSCs in a dose-dependent manner. Pre-treatment with mtROS inhibitor acetyl-L-carnitine (ALCAR, 0.1 mM) significantly inhibited TGF-β1-induced mtROS production and SA-Gal activity.
  
  
  CONCLUSIONS
  TGF-β1 can induce senescence of bmMSCs, which at least partially depends on mtROS production.
authors.forename: Junfang
authors.initials: J
authors.lastname: Wu
authors.forename: Jie
authors.initials: J
authors.lastname: Niu
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Li
authors.forename: Xianwei
authors.initials: X
authors.lastname: Wang
authors.forename: Zhikun
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of Anatomy, Xinxiang Medical University, Xinxiang 453003, China. fxzhang0824@gmail.com.
authors.forename: Fenxi
authors.initials: F
authors.lastname: Zhang
mesh_terms: D000108:Acetylcarnitine / Q000494:pharmacology; D050156:Adipogenesis / Q000187:drug effects; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005696:Galactosidases / Q000378:metabolism; D051798:Inhibitor of Differentiation Protein 1 / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D014803:Vitamin B Complex / Q000494:pharmacology; D000099156:Superoxide Dismutase 2
chemical_list: D000108:Acetylcarnitine; D000447:Aldehydes; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005696:Galactosidases; D051798:Inhibitor of Differentiation Protein 1; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D053773:Transforming Growth Factor beta1; D014803:Vitamin B Complex; D000099156:Superoxide Dismutase 2; C497455:Idb1 protein, mouse; C027576:4-hydroxy-2-nonenal