Aryl hydrocarbon receptor negatively regulates lipid synthesis and involves in cell differentiation of SZ95 sebocytes in vitro
Aryl hydrocarbon receptor negatively regulates lipid synthesis and involves in cell differentiation of SZ95 sebocytes in vitro
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芳基烃受体负向调节脂质合成并参与体外SZ95皮脂细胞的细胞分化
DOI：
10.1016/j.cbi.2016.08.012
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发表时间：
2016-10-25
影响因子：
5.1
通讯作者：
Ju, Qiang
中科院分区：
文献类型：
--
作者：
Hu, Tingting;Wang, Duo;Ju, Qiang
芳烃受体（Aryl烃receptor，AhR）是2，3，7，8-四氯二苯并对二恶英（tetrachlorodibenzo-p-dioxin，TCDD）、苯并（a）芘（benzo（a）pyrene，BaP）等外源性化合物的受体。在人类皮脂腺细胞中，发现TCDD和BaP激活多个基因的表达，包括细胞色素P450 1A 1（CYP 1A 1），并通过AhR抑制脂质合成，而对AhR的内源性功能知之甚少。为了扩展这方面的知识，我们分析了AhR敲低对脂质合成以及对体外SZ 95皮脂腺细胞的细胞分化的影响，并观察到AhR沉默的SZ 95皮脂腺细胞中脂质合成被显著诱导。与此结果一致，脂肪生成相关基因的表达，如过氧化物酶体增殖物激活受体（PPAR）δ和PPAR γ，增加。与AhR激活的细胞相比，AhR沉默的SZ 95皮脂腺细胞中观察到细胞尺寸较小但胞质脂质更丰富的形态变化。此外，角蛋白7，早期皮脂腺分化标志物的表达增加，而终末皮脂细胞分化标志物上皮膜抗原（EMA）的表达减少。此外，终末角质形成细胞分化标志物角蛋白10和外皮蛋白，以及AhR下游蛋白CYP 1A 1在AhR沉默后减少。据我们所知，我们提供的证据表明，在缺乏外源性配体，AhR抑制脂质合成和参与细胞分化的人SZ 95皮脂腺细胞，这表明该受体在人皮脂腺细胞的生理功能。(C)2016爱思唯尔爱尔兰有限公司版权所有。
The aryl hydrocarbon receptor (AhR) is the receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), benzo(a) pyrene (BaP) and other exogenous compounds. In human sebocytes, TCDD and BaP were found to activate the expression of multiple genes, including cytochrome P450 1A1 (CYP1A1), and inhibit lipid synthesis via AhR, while little is known about endogenous functions of the AhR. In order to expand this knowledge, we analyzed the impact of AhR knockdown on lipid synthesis as well as on cell differentiation of SZ95 sebocytes in vitro and observed that lipid synthesis was significantly induced in AhR silenced SZ95 sebocytes. In line with this result, expression of lipogenesis-associated genes, such as peroxisome proliferator activated receptor (PPAR) delta and PPAR gamma, was increased. Morphological changes with smaller cells in size but more abundant cytoplasmic lipids were observed in AhR silenced SZ95 sebocytes compared with the AhR activated cells. Besides, the expression of keratin 7, an early sebaceous differentiation marker, was increased, while the expression of the terminal sebocyte differentiation marker epithelial membrane antigen (EMA) was reduced. Moreover, the terminal keratinocyte differentiation markers keratin 10 and involucrin, and the AhR downstream protein CYP1A1 were reduced after AhR silencing. To the best of our knowledge, we provide evidence that in the absence of exogenous ligands, the AhR inhibits lipid synthesis and involves in cell differentiation of human SZ95 sebocytes, which indicates the physiological function of this receptor in human sebocytes. (C) 2016 Elsevier Ireland Ltd. All rights reserved.