Ultraviolet A irradiation induces senescence in human dermal fibroblasts by down-regulating DNMT1 via ZEB1.
Ultraviolet A irradiation induces senescence in human dermal fibroblasts by down-regulating DNMT1 via ZEB1.
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紫外线 A 照射通过 ZEB1 下调 DNMT1 诱导人真皮成纤维细胞衰老
DOI：
10.18632/aging.101383
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发表时间：
2018-02-16
期刊：
影响因子：
--
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Yi Y;Xie H;Xiao X;Wang B;Du R;Liu Y;Li Z;Wang J;Sun L;Deng Z;Li J
在这项研究中，我们报告了DNA甲基转移酶1（DNMT1）在紫外线A（UVA）诱导的人皮肤成纤维细胞（HDF）衰老中的作用。我们发现，DNMT1的表达显着减少UVA诱导的衰老过程中，这种衰老可以减轻或加重DNMT1的上调或下调，分别。转录因子锌指E盒结合同源异型盒1（ZEB 1）的表达也下降UVA照射后，UVA诱导的细胞内活性氧（ROS）的增加。我们发现，ZEB1结合到DMNT1启动子和调节其转录，这反过来又影响细胞衰老。UVA暴露后DMNT1和ZEB1表达的这些变化在匹配的皮肤样本中得到了证实，这些皮肤样本有或没有暴露在阳光下。通过分析这些匹配皮肤样本中24个衰老相关基因的启动子甲基化，我们发现，暴露于阳光下的皮肤中p53启动子甲基化显著降低。体外实验证实，UVA照射降低了p53启动子甲基化，而DNMT 1上调可逆转这一效应。总之，UVA诱导的ROS下调ZEB 1的表达，可抑制DNMT 1的转录，导致衰老相关蛋白p53甲基化水平降低，并增加其表达，最终导致细胞衰老。
In this study, we report the role of DNA methyltransferase 1 (DNMT1) in ultraviolet A (UVA)-induced senescence in human dermal fibroblasts (HDFs). We show that DNMT1 expression was significantly reduced during UVA-induced senescence, and this senescence could be alleviated or aggravated by the up- or down-regulation of DNMT1, respectively. Expression of the transcription factor zinc finger E-box binding homeobox 1(ZEB1) also decreased after UVA irradiation, following a UVA-induced increase of intracellular reactive oxygen species (ROS). We show that ZEB1 binds to the DMNT1 promoter and regulates its transcription, which, in turn, affects cellular senescence. These changes in DMNT1 and ZEB1 expression following UVA exposure were confirmed in matched skin specimens that had or had not been sun-exposed. On analyzing the promoter methylation of 24 senescence associated genes in these matched skin specimens, we discovered that p53 promoter methylation was significantly reduced in sun-exposed skin. In vitro experiments confirmed that UVA irradiation reduced p53 promoter methylation, and DNMT1 up-regulation could reverse this effect. Collectively, down-regulation of ZEB1 caused by UVA induced ROS could transcriptionally inhibit DNMT1, leading to low methylation level of senescence related proteins p53 and increase its expression, eventually result in cellar senescence.
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影响因子：
64.5
作者：
López-Otín C;Blasco MA;Partridge L;Serrano M;Kroemer G
通讯作者：
Kroemer G
DNA甲基化模式和转录连通性降低定义了人皮肤老化。
影响因子：
7.8
作者：
Bormann F;Rodríguez-Paredes M;Hagemann S;Manchanda H;Kristof B;Gutekunst J;Raddatz G;Haas R;Terstegen L;Wenck H;Kaderali L;Winnefeld M;Lyko F
通讯作者：
Lyko F
影响因子：
11.2
作者：
Ohashi S;Natsuizaka M;Wong GS;Michaylira CZ;Grugan KD;Stairs DB;Kalabis J;Vega ME;Kalman RA;Nakagawa M;Klein-Szanto AJ;Herlyn M;Diehl JA;Rustgi AK;Nakagawa H
通讯作者：
Nakagawa H
DOI：
10.1038/skinbio.2013.176
发表时间：
2013-07-01
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
Gilchrest, Barbara A
通讯作者：
Gilchrest, Barbara A
ΔEF1与DNMT1相关，并维持乳腺癌细胞中电子钙粘蛋白启动子的DNA甲基化。
影响因子：
4
作者：
Fukagawa, Akihiko;Ishii, Hiroki;Miyazawa, Keiji;Saitoh, Masao
通讯作者：
Saitoh, Masao