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UNC5B Promotes Vascular Endothelial Cell Senescence via the ROS-Mediated P53 Pathway

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单位: [1]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Geriatr, Wuhan 430030, Hubei, Peoples R China
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Vascular endothelial cell senescence is involved in human aging and age-related vascular disorders. Guidance receptor UNC5B is implicated in oxidative stress and angiogenesis. Nonetheless, little is known about the role of UNC5B in endothelial cell senescence. Here, we cultured primary human umbilical vein endothelial cells to young and senescent phases. Subsequently, the expression of UNC5B was identified in replicative senescent cells, and then, its effect on endothelial cell senescence was confirmed by UNC5B-overexpressing lentiviral vectors and RNA interference. Overexpression of UNC5B in young endothelial cells significantly increased senescence-associated beta-galactosidase-positive cells, upregulated the mRNAs expression of the senescence-associated secretory phenotype genes, reduced total cell number, and inhibited the potential for cell proliferation. Furthermore, overexpression of UNC5B promoted the generation of intracellular reactive oxygen species (ROS) and activated the P53 pathway. Besides, overexpression of UNC5B disturbed endothelial function by inhibiting cell migration and tube formation. Nevertheless, silencing UNC5B generated conflicting outcomes. Blocking ROS production or inhibiting the function of P53 rescued endothelial cell senescence induced by UNC5B. These findings suggest that UNC5B promotes endothelial cell senescence, potentially by activating the ROS-P53 pathway. Therefore, inhibiting UNC5B might reduce endothelial cell senescence and hinder age-related vascular disorders.

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大类 | 2 区 生物
小类 | 3 区 细胞生物学
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Q2 CELL BIOLOGY
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第一作者单位: [1]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Geriatr, Wuhan 430030, Hubei, Peoples R China
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