光老化
基质金属蛋白酶
哈卡特
DNA损伤
芳香烃受体
化学
MMP1型
细胞生物学
皱纹
MMP9公司
皮肤老化
MMP2型
早衰
癌症研究
转录因子
人体皮肤
细胞外基质
下调和上调
生物
生物化学
医学
DNA
皮肤病科
基因表达
遗传学
体外
基因
作者
Daniel J. Kim,Akiko Iwasaki,Anna L. Chien,Sewon Kang
出处
期刊:JCI insight
[American Society for Clinical Investigation]
日期:2022-05-09
卷期号:7 (9)
被引量:32
标识
DOI:10.1172/jci.insight.156344
摘要
It is currently thought that UVB radiation drives photoaging of the skin primarily by generating ROS. In this model, ROS purportedly activates activator protein-1 to upregulate MMPs 1, 3, and 9, which then degrade collagen and other extracellular matrix components to produce wrinkles. However, these MMPs are expressed at relatively low levels and correlate poorly with wrinkles, suggesting that another mechanism distinct from ROS and MMP1/3/9 may be more directly associated with photoaging. Here we show that MMP2, which degrades type IV collagen, is abundantly expressed in human skin, increases with age in sun-exposed skin, and correlates robustly with aryl hydrocarbon receptor (AhR), a transcription factor directly activated by UV-generated photometabolites. Through mechanistic studies with HaCaT human immortalized keratinocytes, we found that AhR, specificity protein 1 (SP1), and other pathways associated with DNA damage are required for the induction of both MMP2 and MMP11 (another MMP implicated in photoaging), but not MMP1/3. Last, we found that topical treatment with AhR antagonists vitamin B12 and folic acid ameliorated UVB-induced wrinkle formation in mice while dampening MMP2 expression in the skin. These results directly implicate DNA damage in photoaging and reveal AhR as a potential target for preventing wrinkles.
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