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ZNPs 通过 mTORC1-TFEB-BLOC1S3 轴促进桥粒钙黏附蛋白内吞作用来降低表皮机械应变阻力。

ZNPs reduce epidermal mechanical strain resistance by promoting desmosomal cadherin endocytosis via mTORC1-TFEB-BLOC1S3 axis.

机构信息

Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, 510515, China.

Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.

出版信息

J Nanobiotechnology. 2024 Jun 5;22(1):312. doi: 10.1186/s12951-024-02519-z.

DOI:10.1186/s12951-024-02519-z
PMID:38840221
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11151536/
Abstract

Zinc oxide nanoparticles (ZNPs) are widely used in sunscreens and nanomedicines, and it was recently confirmed that ZNPs can penetrate stratum corneum into deep epidermis. Therefore, it is necessary to determine the impact of ZNPs on epidermis. In this study, ZNPs were applied to mouse skin at a relatively low concentration for one week. As a result, desmosomes in epidermal tissues were depolymerized, epidermal mechanical strain resistance was reduced, and the levels of desmosomal cadherins were decreased in cell membrane lysates and increased in cytoplasmic lysates. This finding suggested that ZNPs promote desmosomal cadherin endocytosis, which causes desmosome depolymerization. In further studies, ZNPs were proved to decrease mammalian target of rapamycin complex 1 (mTORC1) activity, activate transcription factor EB (TFEB), upregulate biogenesis of lysosome-related organelle complex 1 subunit 3 (BLOC1S3) and consequently promote desmosomal cadherin endocytosis. In addition, the key role of mTORC1 in ZNP-induced decrease in mechanical strain resistance was determined both in vitro and in vivo. It can be concluded that ZNPs reduce epidermal mechanical strain resistance by promoting desmosomal cadherin endocytosis via the mTORC1-TFEB-BLOC1S3 axis. This study helps elucidate the biological effects of ZNPs and suggests that ZNPs increase the risk of epidermal fragmentation.

摘要

氧化锌纳米粒子(ZNPs)广泛应用于防晒霜和纳米药物中,最近有研究证实 ZNPs 可以穿透角质层进入深部表皮。因此,有必要确定 ZNPs 对表皮的影响。在这项研究中,将 ZNPs 以相对较低的浓度应用于小鼠皮肤一周。结果表明,表皮组织中的桥粒解聚,表皮机械应变阻力降低,细胞膜裂解液中桥粒钙黏蛋白水平降低,细胞质裂解液中桥粒钙黏蛋白水平升高。这表明 ZNPs 促进桥粒钙黏蛋白内吞作用,导致桥粒解聚。进一步的研究表明,ZNPs 降低了哺乳动物雷帕霉素靶蛋白复合物 1(mTORC1)的活性,激活转录因子 EB(TFEB),上调溶酶体相关细胞器复合物 1 亚基 3(BLOC1S3)的生物发生,从而促进桥粒钙黏蛋白内吞作用。此外,在体外和体内均证实了 mTORC1 在 ZNP 诱导的机械应变阻力降低中的关键作用。可以得出结论,ZNPs 通过 mTORC1-TFEB-BLOC1S3 轴促进桥粒钙黏蛋白内吞作用,从而降低表皮的机械应变阻力。本研究有助于阐明 ZNPs 的生物学效应,并表明 ZNPs 增加了表皮碎片的风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc93/11151536/d061f2e45536/12951_2024_2519_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc93/11151536/d061f2e45536/12951_2024_2519_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc93/11151536/7f4d2dd809cb/12951_2024_2519_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc93/11151536/db21d85aaa6d/12951_2024_2519_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc93/11151536/eaad0e8472ab/12951_2024_2519_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc93/11151536/03b245e9e7f2/12951_2024_2519_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc93/11151536/d061f2e45536/12951_2024_2519_Fig7_HTML.jpg

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本文引用的文献

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