Local Epidermal Endocrine Estrogen Protects Human Melanocytes against Oxidative Stress, a Novel Insight into Vitiligo Pathology.
Local Epidermal Endocrine Estrogen Protects Human Melanocytes against Oxidative Stress, a Novel Insight into Vitiligo Pathology.
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DOI：
10.3390/ijms22010269
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发表时间：
2020-12-29
影响因子：
5.6
通讯作者：
Katayama I
中科院分区：
文献类型：
--
作者：
Yamamoto A;Yang L;Kuroda Y;Guo J;Teng L;Tsuruta D;Katayama I
皮肤作为人体最外层的屏障，是氧化应激的主要目标。据报道，在大脑中，雌激素是在局部合成的，可以保护神经元免受氧化应激。在这里，我们探索了雌激素是否也在皮肤局部合成以保护免受氧化应激，以及局部雌激素异常合成是否与皮肤疾病有关。用实时定量聚合酶链式反应和免疫印迹分析检测皮肤细胞中的酶和雌激素受体的表达。有趣的是，在13种培养的人皮肤细胞中，雌激素合成酶主要定位于表皮角质形成细胞，雌激素受体主要表达于黑素细胞。表皮中表达最丰富的雌激素合成酶是角质形成细胞中表达的17β-羟基类固醇脱氢酶1(17β1)，黑素细胞中最主要的雌激素受体是G蛋白偶联雌激素受体1(GPER1)。为探讨角质形成细胞衍生的雌二醇是否具有保护黑素细胞免受氧化应激的作用，将体外培养的人原代表皮黑素细胞(HEMN-MPS)在含或不含17β雌二醇的条件下用过氧化氢处理，或与转HSD17β1siRNA的角质形成细胞共培养。角质形成细胞衍生的雌二醇对H_2O_2诱导的细胞死亡具有保护作用。此外，与健康供者的皮肤或白癜风患者正常皮肤部分相比，白癜风患者皮肤表皮中HSD17β1的表达减少。我们的研究结果为白癜风患者的干预提供了一个可能的新靶点，该靶点可以与目前的治疗方法结合使用。
As the outermost barrier of the body, skin is a major target of oxidative stress. In the brain, estrogen has been reported synthesized locally and protects neurons from oxidative stress. Here, we explored whether estrogen is also locally synthesized in the skin to protect from oxidative stress and whether aberrant local estrogen synthesis is involved in skin disorders. Enzymes and estrogen receptor expression in skin cells were examined first by quantitative real-time PCR and Western blot analyses. Interestingly, the estrogen synthesis enzyme was mainly localized in epidermal keratinocytes and estrogen receptors were mainly expressed in melanocytes among 13 kinds of cultured human skin cells. The most abundant estrogen synthesis enzyme expressed in the epidermis was 17β-hydroxysteroid dehydrogenase 1 (HSD17β1) localized in keratinocytes, and the most dominant estrogen receptor expressed in the epidermis was G protein-coupled estrogen receptor 1 (GPER1) in melanocytes. To investigate whether keratinocyte-derived estradiol could protect melanocytes from oxidative stress, cultured human primary epidermal melanocytes (HEMn-MPs) were treated with H2O2 in the presence or absence of 17β estradiol or co-cultured with HSD17β1 siRNA-transfected keratinocytes. Keratinocyte-derived estradiol exhibited protective effects against H2O2-induced cell death. Further, reduced expression of HSD17β1 in the epidermis of skin from vitiligo patients was observed compared to the skin from healthy donors or in the normal portions of the skin in vitiligo patients. Our results suggest a possible new target for interventions that may be used in combination with current therapies for patients with vitiligo.
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影响因子：
11.4
作者：
Bellanti F;Matteo M;Rollo T;De Rosario F;Greco P;Vendemiale G;Serviddio G
通讯作者：
Serviddio G
影响因子：
6.5
作者：
Schallreuter, Karin U.;Chiuchiarelli, Georgia;Anderson, Diana
通讯作者：
Anderson, Diana
DOI：
10.1073/pnas.96.16.8867
发表时间：
1999-08-03
影响因子：
11.1
作者：
Moosmann, B;Behl, C
通讯作者：
Behl, C
影响因子：
6.5
作者：
Denat, Laurence;Kadekaro, Ana L.;Marrot, Laurent;Leachman, Sancy A.;Abdel-Malek, Zalfa A.
通讯作者：
Abdel-Malek, Zalfa A.
影响因子：
20.1
作者：
Strehlow, K;Rotter, S;Nickenig, G
通讯作者：
Nickenig, G