Keratin 17 Is Required for Lipid Metabolism in Keratinocytes and Benefits Epidermal Permeability Barrier Homeostasis.
Keratin 17 Is Required for Lipid Metabolism in Keratinocytes and Benefits Epidermal Permeability Barrier Homeostasis.
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DOI：
10.3389/fcell.2021.779257
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发表时间：
2021
影响因子：
5.5
通讯作者：
Wang G
中科院分区：
文献类型：
--
作者：
Pang B;Zhu Z;Xiao C;Luo Y;Fang H;Bai Y;Sun Z;Ma J;Dang E;Wang G
表皮屏障是指皮肤最上层的角质层，构成了抵御潜在有害病原体入侵的第一道防线，减少了经表皮的水分损失，在维持皮肤动态平衡方面起着至关重要的作用。角蛋白17(keratin17，K17)是一种I型上皮角蛋白，具有多种功能，包括在皮肤炎症、上皮细胞生长、蛋白质合成和肿瘤发生中的作用。然而，K17与皮肤屏障的关系尚未得到系统的研究。在本研究中，我们发现，急性破坏表皮通透性屏障导致体内表皮K17表达迅速增加。Krt17基因缺陷导致小鼠脂代谢相关酶和抗菌肽表达减少，同时也延缓了急性损伤后表皮通透性屏障的恢复。腺病毒介导的K17过表达增强，而小干扰RNA介导的Krt17抑制脂肪酸合成酶、转录因子SREBP-1和PPARγ的表达。我们进一步证实K17可以促进角质形成细胞中SREBP-1和PPARγ的核转运和促进脂质的合成。这项研究表明，K17通过稳定角质形成细胞中的脂质代谢，有助于表皮通透性屏障的恢复。
The epidermal barrier refers to the stratum corneum, the uppermost layer of the skin, and constitutes the first line of defense against invasion by potentially harmful pathogens, diminishes trans-epidermal water loss, and plays a crucial role in the maintenance of skin homeostasis. Keratin 17 (K17) is a type I epithelial keratin with multiple functions, including in skin inflammation, epithelial cell growth, protein synthesis, and tumorigenesis. However, the relationship between K17 and the skin barrier has yet to be systematically investigated. In this study, we found that acute disruption of the epidermal permeability barrier led to a rapid increase in epidermal K17 expression in vivo. Krt17 gene deficiency in mice resulted in decreased expression of lipid metabolism-related enzymes and antimicrobial peptides, while also delaying epidermal permeability barrier recovery after acute disruption. Adenovirus-mediated overexpression of K17 enhanced, whereas siRNA-mediated knockdown of Krt17 inhibited, the expression of fatty acid synthase (FASN) and that of the transcription factors SREBP-1 and PPARγ in vitro. We further confirmed that K17 can facilitate the nuclear transportation of SREBP-1 and PPARγ and promote lipid synthesis in keratinocytes. This study demonstrated that K17 contributes to the restoration of the epidermal permeability barrier via stabilizing lipid metabolism in keratinocytes.
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DOI：
10.1016/j.jid.2017.01.007
发表时间：
2017-06
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
Hu L;Mauro TM;Dang E;Man G;Zhang J;Lee D;Wang G;Feingold KR;Elias PM;Man MQ
通讯作者：
Man MQ
影响因子：
64.8
作者：
Kim, S;Wong, P;Coulombe, PA
通讯作者：
Coulombe, PA
影响因子：
6.5
作者：
Jiang, Yan J.;Lu, Biao;Feingold, Kenneth R.
通讯作者：
Feingold, Kenneth R.
影响因子：
16
作者：
Düvel K;Yecies JL;Menon S;Raman P;Lipovsky AI;Souza AL;Triantafellow E;Ma Q;Gorski R;Cleaver S;Vander Heiden MG;MacKeigan JP;Finan PM;Clish CB;Murphy LO;Manning BD
通讯作者：
Manning BD
影响因子：
6.5
作者：
Man, Mao-Qiang;Choi, Eung-Ho;Feingold, Kenneth R.
通讯作者：
Feingold, Kenneth R.