Aging-like skin changes in metabolic syndrome model mice are mediated by mineralocorticoid receptor signaling
Aging-like skin changes in metabolic syndrome model mice are mediated by mineralocorticoid receptor signaling
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DOI：
10.1111/acel.12017
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发表时间：
2013-02-01
期刊：
影响因子：
7.8
通讯作者：
Sugama, Junko
中科院分区：
文献类型：
--
作者：
Nagase, Takashi;Akase, Tomoko;Sugama, Junko
衰老至少部分地由病理状况如代谢综合征（MetS）加速，并且各种分子途径如氧化应激是衰老和MetS的常见介质。我们先前通过单次紫外线（UV）照射MetS模型小鼠建立了类衰老皮肤模型。近年来的研究表明，盐皮质激素受体（MR）信号在代谢综合征的各种组织炎症和损伤中起着关键作用。虽然先前的研究报道了MR在皮肤中表达，并且MR在皮肤中的过度表达导致皮肤萎缩，但MR在皮肤中的生理或病理功能尚未完全阐明。在这里，我们展示了MR信号在我们自己的模型中参与衰老样皮肤变化。在MetS小鼠中观察到氧化应激和炎症标志物的升高，并且通过局部抗氧化剂减轻UV诱发的老化样皮肤损伤。MR在MetS小鼠皮肤中的表达更高，并且值得注意的是，其效应基因Sgk1的表达在UV照射的MetS小鼠的衰老样皮肤中显著上调。此外，局部应用MR拮抗剂螺内酯抑制Sgk1表达，氧化应激，炎症和皮肤的老化样变化。非MetS小鼠的2周UV照射，更常见的光老化模型，导致的皮肤损伤与单次UV照射的MetS小鼠相当，但它们与MR信号的上调无关。我们的研究表明MR信号在MetS状态下的皮肤衰老中具有意想不到的作用。
Aging is accelerated, at least in part, by pathological condition such as metabolic syndrome (MetS), and various molecular pathways such as oxidative stress are common mediators of aging and MetS. We previously developed the aging-like skin model by single ultraviolet (UV) irradiation on the MetS model mice. Recent studies revealed that mineralocorticoid receptor (MR) signaling plays a pivotal role for various tissue inflammation and damages in MetS. Although previous studies reported that MR is expressed in the skin and that overexpression of MR in the skin resulted in the skin atrophy, the physiological or pathological functions of MR in the skin are not fully elucidated. Here, we show the involvement of MR signaling in the aging-like skin changes in our own model. Elevations of oxidative stress and inflammation markers were observed in the MetS mice, and the UV-evoked aging-like skin damages were attenuated by topical antioxidant. MR expression was higher in the MetS mouse skin, and notably, expression of its effecter gene Sgk1 was significantly upregulated in the aging-like skin in the UV-irradiated MetS mice. Furthermore, topical application of MR antagonist spironolactone suppressed Sgk1 expression, oxidative stress, inflammation, and the aging-like changes in the skin. The 2-week UV onto the non-MetS mice, the more usual photoaging model, resulted in the skin damages mostly equivalent to the MetS mice with single UV, but they were not associated with upregulation of MR signaling. Our studies suggested an unexpected role of MR signaling in the skin aging in MetS status.