دورية أكاديمية

Alteration of E2F2 Expression in Governing Endothelial Cell Senescence.

التفاصيل البيبلوغرافية
العنوان: Alteration of E2F2 Expression in Governing Endothelial Cell Senescence.
المؤلفون: Liu H; Vascular Function Laboratory, Human Aging Research Institute and School of Life Science, Jiangxi Key Laboratory of Human Aging, Nanchang University, Nanchang 330031, China., Chen L; Vascular Function Laboratory, Human Aging Research Institute and School of Life Science, Jiangxi Key Laboratory of Human Aging, Nanchang University, Nanchang 330031, China., Xiao W; Metabolic Control and Aging, Human Aging Research Institute and School of Life Science, Jiangxi Key Laboratory of Human Aging, Nanchang University, Nanchang 330031, China., Liu J; Aging and Vascular Diseases, Human Aging Research Institute and School of Life Science, Jiangxi Key Laboratory of Human Aging, Nanchang University, Nanchang 330031, China., Long C; Vascular Function Laboratory, Human Aging Research Institute and School of Life Science, Jiangxi Key Laboratory of Human Aging, Nanchang University, Nanchang 330031, China., Zhan W; Vascular Function Laboratory, Human Aging Research Institute and School of Life Science, Jiangxi Key Laboratory of Human Aging, Nanchang University, Nanchang 330031, China., Cui C; Department of Ophthalmology, Handan Central Hospital, Handan 056001, China., Yang L; Department of Nephrology, Taikang Southwestern Medical Center, Chengdu 610213, China., Chen S; Vascular Function Laboratory, Human Aging Research Institute and School of Life Science, Jiangxi Key Laboratory of Human Aging, Nanchang University, Nanchang 330031, China.
المصدر: Genes [Genes (Basel)] 2022 Aug 24; Vol. 13 (9). Date of Electronic Publication: 2022 Aug 24.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101551097 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4425 (Electronic) Linking ISSN: 20734425 NLM ISO Abbreviation: Genes (Basel) Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel : MDPI
مواضيع طبية MeSH: Cellular Senescence*/genetics , E2F2 Transcription Factor*/genetics , E2F2 Transcription Factor*/metabolism , Nitric Oxide Synthase Type III*/metabolism , Sirtuin 1*/genetics, Animals ; Cells, Cultured ; Human Umbilical Vein Endothelial Cells/metabolism ; Humans ; Interleukin-6 ; Interleukin-8 ; Mice ; beta-Galactosidase
مستخلص: Endothelial cell senescence has a vital implication for vascular dysfunction, leading to age-related cardiovascular disease, especially hypertension and atherosclerosis. E2F transcription factor 2 (E2F2) plays a critical role in cell proliferation, differentiation, and DNA damage response. Up to date, no study has ever connected E2F2 to vascular endothelial cell senescence. Here, we demonstrate that E2F2 is involved in endothelial cellular senescence. We found that E2F2 expression is decreased during the replicative senescence of human umbilical vein endothelial cells (HUVECs) and the aortas of aged mice. The knockdown of E2F2 in young HUVECs induces premature senescence characterized by an increase in senescence-associated β-galactosidase (SA-β-gal) activity, a reduction in phosphorylated endothelial nitric oxide synthase (p-eNOS) and sirtuin 1 (SIRT1), and the upregulation of senescence-associated secretory phenotype (SASP) IL-6 and IL-8. The lack of E2F2 promoted cell cycle arrest, DNA damage, and cell proliferation inhibition. Conversely, E2F2 overexpression reversed the senescence phenotype and enhanced the cellular function in the senescent cells. Furthermore, E2F2 deficiency downregulated downstream target genes including CNNA2, CDK1, and FOXM1, and overexpression restored the expression of these genes. Our findings demonstrate that E2F2 plays an indispensable role in endothelial cell senescence.
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فهرسة مساهمة: Keywords: E2F2; cell cycle; endothelial cell; proliferation; senescence
المشرفين على المادة: 0 (E2F2 Transcription Factor)
0 (E2F2 protein, human)
0 (Interleukin-6)
0 (Interleukin-8)
EC 1.14.13.39 (Nitric Oxide Synthase Type III)
EC 3.2.1.23 (beta-Galactosidase)
EC 3.5.1.- (Sirtuin 1)
تواريخ الأحداث: Date Created: 20220923 Date Completed: 20220926 Latest Revision: 20221007
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC9498592
DOI: 10.3390/genes13091522
PMID: 36140689
قاعدة البيانات: MEDLINE
الوصف
تدمد:2073-4425
DOI:10.3390/genes13091522