Iron sensitizes keratinocytes and fibroblasts to UVA-mediated matrix metalloproteinase-1 through TNF-α and ERK activation.
Iron sensitizes keratinocytes and fibroblasts to UVA-mediated matrix metalloproteinase-1 through TNF-α and ERK activation.
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DOI：
10.1111/j.1600-0625.2010.01152.x
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发表时间：
2011-03
影响因子：
3.6
通讯作者：
Huang X
中科院分区：
文献类型：
--
作者：
Jian J;Pelle E;Yang Q;Pernodet N;Maes D;Huang X
雌激素缺乏被认为是绝经后皮肤老化和光老化的主要原因。虽然绝经后的妇女由于卵巢功能停止而经历低水平的雌激素，但由于月经停止，她们也暴露于高水平的铁。在这项研究中，我们调查了铁的增加是否会对绝经后皮肤造成风险。由于缺乏合适的动物模型来密切模拟低雌激素和高铁条件，我们测试了高铁和低雌激素培养模型的假设。在这里，我们表明，原代人皮肤成纤维细胞暴露于铁不影响基质金属蛋白酶-1（MMP-1）活性的基线水平。然而，铁暴露的成纤维细胞对UVA暴露敏感，这导致MMP-1的协同增加。UVA激活MAPK家族的三个成员：ERK、p38和JNKs。铁对ERK的额外激活有助于协同增加。原代正常人表皮角质形成细胞（NHEK）对铁或UVA暴露没有反应，但在培养基中产生肿瘤坏死因子-α（TNF-α），然后刺激成纤维细胞中的MMP-1。我们的研究结果表明，铁和UVA增加MMP-1活性在真皮成纤维细胞不仅直接通过ERK激活，但也通过间接旁分泌环通过TNF-α释放的NHEK。我们的结论是，除了雌激素缺乏，增加铁作为一个结果，绝经可能是一个新的危险因素，通过敏感绝经后皮肤太阳辐射。
Oestrogen deficiency is regarded as the main causative factor in postmenopausal skin ageing and photoageing. While women after menopause experience low levels of oestrogen because of cease of ovarian function, they are also exposed to high levels of iron as a result of cessation of menstruation. In this study, we investigated whether this increase in iron presents a risk to the postmenopausal skin. Because of the lack of appropriate animal models to closely mimic the low oestrogen and high iron conditions, we tested the hypothesis in a high iron and low oestrogen culture model. Here, we showed that primary human dermal fibroblasts exposed to iron did not affect the baseline levels of matrix metalloproteinase-1 (MMP-1) activity. However, the iron-exposed fibroblasts were sensitized to UVA exposure, which resulted in a synergistic increase in MMP-1. UVA activated the three members of MAPK family: ERKs, p38, and JNKs. Additional activation of ERKs by iron contributed to the synergistic increases. Primary normal human epidermal keratinocytes (NHEK) did not respond to iron or UVA exposure as measured by MMP-1, but produced tumor necrosis factor-alpha (TNF-α) in the media, which then stimulated MMP-1 in fibroblasts. Our results indicate that iron and UVA increase MMP-1 activity in dermal fibroblasts not only directly through ERK activation but also by an indirect paracrine loop through TNF-α released by NHEK. We conclude that in addition to oestrogen deficiency, increased iron as a result of menopause could be a novel risk factor by sensitizing postmenopausal skin to solar irradiation.
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DOI：
10.1152/ajpheart.00928.2007
发表时间：
2007-12-01
影响因子：
4.8
作者：
Cortez, Dolores M.;Feldman, Marc D.;Chandrasekar, Bysani
通讯作者：
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影响因子：
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作者：
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影响因子：
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10.1038/sj.jidsymp.5650008
发表时间：
2006-09-01
影响因子：
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作者：
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通讯作者：
Saunders, W. Brian
影响因子：
3.8
作者：
Kida, Y;Kobayashi, M;Hasegawa, K
通讯作者：
Hasegawa, K