title: Nox2 and Nox4 regulate self-renewal of murine induced-pluripotent stem cells.
abstract: Reactive oxygen species (ROS) and redox homeostasis have a pivotal role in the maintenance of stem cell pluripotency and in stem cell self-renewal; however, the mechanisms by which ROS regulate the self-renewal of stem cells have not been thoroughly studied. Here, we evaluated the role of the ROS produced by NADPH oxidase 2 (Nox2) and NADPH oxidase 4 (Nox4) in the self-renewal and stemness of murine induced-pluripotent stem cells (miPSCs). Targeted silencing of Nox2 or Nox4 reduced both NADPH oxidase activity and intracellular ROS levels, as well as alkaline phosphatase activity, the total number of miPSCs, the expression of insulin-like growth factor-1 (IGF-1), IGF-1 receptor, and the phosphorylation of extracellular signal regulated kinase (ERK) 1/2. Nox2/Nox4 overexpression or low, nontoxic concentration of H2O2increased cell proliferation in miPSCs. Furthermore, expression of the stemness genes Sox2 and Oct4 was lower in Nox2/Nox4-deficient miPSCs, and higher in Nox2/Nox4-overexpressing miPSCs, than in miPSCs with normal levels of Nox2/Nox4 expression. Collectively, these results suggest that Nox2- and Nox4-derived ROS contribute to stem cell pluripotency maintenance and self-renewal. © 2016 IUBMB Life, 68(12):963-970, 2016.
authors: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors: Xueling
authors: X
authors: Kang
authors: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors: Xiangxiang
authors: X
authors: Wei
authors: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors: Li
authors: L
authors: Jiang
authors: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors: Cong
authors: C
authors: Niu
authors: Department of Biomedical Engineering, School of Medicine, University of Alabama at Birmingham, Birmingham, AL.
authors: Jianyi
authors: J
authors: Zhang
authors: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors: Sifeng
authors: S
authors: Chen
authors: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors: Dan
authors: D
authors: Meng
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D000066673:Cell Self Renewal; D002478:Cells, Cultured; D055785:Gene Knockdown Techniques; D057026:Induced Pluripotent Stem Cells / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C422943:Nox4 protein, mouse
keywords: Nox2; Nox4; reactive oxygen species; self-renewal; stem cell