The pivotal role of reactive oxygen species generation in the hypoxia-induced stimulation of adipose-derived stem cells.
Adipose-derived stem cells (ASCs) offer a potential alternative for tissue repair and regeneration. We have recently shown that hypoxia stimulates ASCs and enhances the regenerative potential of ASCs, which is beneficial for ASC therapy. In the present study, we further investigated a key mediator and a signal pathway involved in the stimulation of ASC during hypoxia. Culturing ASC in a hypoxic incubator (2% oxygen tension) increased the proliferation and migration, and this was mediated by Akt and ERK pathways. To determine the generation of reactive oxygen species (ROS), 2',7'-dichlorofluorescin diacetate intensity was detected by fluorescence-activated cell sorting. Hypoxia significantly increased the dichlorofluorescin diacetate intensity, which was greatly reduced by N-acetyl-cysteine and diphenyleneiodonium treatment. Likewise, the hypoxia-induced proliferation and migration of ASCs were reversed by N-acetyl-cysteine and diphenyleneiodonium treatment, suggesting the involvement of ROS generation in ASC stimulation. Further, we examined the activation of receptor tyrosine kinases and observed that hypoxia stimulated the phosphorylation of platelet-derived growth factor receptor-β. In summary, the ROS produced by ASCs in response to hypoxia was mostly likely due to NADPH oxidase activity. The increased cellular ROS was accompanied by the phosphorylation of platelet-derived growth factor receptor-β as well as by the activation of ERK and Akt signal pathways. Our results suggest a pivotal role for ROS generation in the stimulation of ASCs by hypoxia.
Department of Applied Bioscience, CHA University, Seoul, Korea.
Ji Hye
JH
Kim
So-Hyun
SH
Park
Sang Gyu
SG
Park
Joon-Seok
JS
Choi
Ying
Y
Xia
Jong-Hyuk
JH
Sung
D000273:Adipose Tissue / Q000473:pathology*; D015687:Cell Hypoxia; D002465:Cell Movement; D049109:Cell Proliferation; D005452:Fluoresceins / Q000378:metabolism; D006801:Humans; D019255:NADPH Oxidases / Q000378:metabolism; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D013234:Stem Cells / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D014945:Wound Healing
D005452:Fluoresceins; D017382:Reactive Oxygen Species; C029569:diacetyldichlorofluorescein; D019255:NADPH Oxidases; D020797:Receptor, Platelet-Derived Growth Factor beta
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