Unveiling senescence-associated secretory phenotype in epidermal aging: insights from reversibly immortalized keratinocytes.

IF 3.9 3区 医学 Q2 CELL BIOLOGY Aging-Us Pub Date : 2024-09-23 DOI:10.18632/aging.206117
Lu-Wen Xu, Yi-Dan Sun, Qiao-Yu Fu, Dan Wu, Jian Lin, Chen Wang, Liang Zhang, Cai-Yue Liu, Qing-Feng Li
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Abstract

Aging of epidermal keratinocytes profoundly impacts skin health, contributing to changes in appearance, barrier function, and susceptibility to diseases. Despite its significance, the molecular mechanisms underlying epidermal aging remain elusive. In this study, a reversible immortalized cell line was established by expressing SV40T in keratinocytes using the Tet-Off lentiviral system. Inducing a senescent phenotype by terminating SV40T expression revealed a significant reduction in mitotic ability, as well as characteristics of cellular aging. RNA sequencing analysis revealed alterations in gene expression and signaling pathways including DNA repair dysfunction, notably senescence-associated secretory phenotype (SASP)-related genes, such as MMP1, SERPINB2 and VEGFA. Our study provides insights into the molecular mechanisms of epidermal aging, offering potential therapeutic targets and highlighting the role of SASP in the aging process.

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揭示表皮老化过程中与衰老相关的分泌表型:可逆永生化角质形成细胞的启示
表皮角质细胞的老化会严重影响皮肤健康,导致皮肤外观、屏障功能和疾病易感性发生变化。尽管表皮老化具有重要意义,但其分子机制仍然难以捉摸。在这项研究中,通过使用 Tet-Off 慢病毒系统在角质形成细胞中表达 SV40T,建立了一种可逆的永生化细胞系。通过终止 SV40T 的表达来诱导衰老表型,结果发现细胞有丝分裂能力显著下降,并显示出细胞衰老的特征。RNA 测序分析显示了基因表达和信号通路的改变,包括 DNA 修复功能障碍,尤其是衰老相关分泌表型(SASP)相关基因,如 MMP1、SERPINB2 和 VEGFA。我们的研究深入揭示了表皮老化的分子机制,提供了潜在的治疗靶点,并强调了 SASP 在老化过程中的作用。
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来源期刊
Aging-Us
Aging-Us CELL BIOLOGY-
CiteScore
10.00
自引率
0.00%
发文量
595
审稿时长
6-12 weeks
期刊介绍: Information not localized
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