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Interaction of TAGLN and USP1 promotes ZEB1 ubiquitination degradation in UV-induced skin photoaging

BACKGROUND: Ultraviolet A (UVA) irradiation can lead to skin damage and premature skin aging known as photoaging. This work found that UVA irradiation caused an imbalance between dermal matrix synthesis and degradation through the aberrant upregulation of transgelin (TAGLN) and studied the underlyin...

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Autores principales: Li, Yinan, Huang, Xiu, Jin, Jing, Zhang, Haohao, Yang, Kai, Han, Jingxia, Lv, Ying, Sun, Yu, Yao, Cheng, Lin, Tingting, Zhu, Caibin, Liu, Huijuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10163745/
https://www.ncbi.nlm.nih.gov/pubmed/37149635
http://dx.doi.org/10.1186/s13578-023-01029-z
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author Li, Yinan
Huang, Xiu
Jin, Jing
Zhang, Haohao
Yang, Kai
Han, Jingxia
Lv, Ying
Sun, Yu
Yao, Cheng
Lin, Tingting
Zhu, Caibin
Liu, Huijuan
author_facet Li, Yinan
Huang, Xiu
Jin, Jing
Zhang, Haohao
Yang, Kai
Han, Jingxia
Lv, Ying
Sun, Yu
Yao, Cheng
Lin, Tingting
Zhu, Caibin
Liu, Huijuan
author_sort Li, Yinan
collection PubMed
description BACKGROUND: Ultraviolet A (UVA) irradiation can lead to skin damage and premature skin aging known as photoaging. This work found that UVA irradiation caused an imbalance between dermal matrix synthesis and degradation through the aberrant upregulation of transgelin (TAGLN) and studied the underlying molecular mechanism. RESULTS: Co-immunoprecipitation and proximal ligation assay results showed that TAGLN can interact with USP1. USP1 can be retained in the cytoplasm by TAGLN in UVA-induced cells, which inhibits the interaction between USP1/zinc finger E-box binding homeobox 1 (ZEB1), promote the ubiquitination degradation of ZEB1, and lead to photoaging. TAGLN knockdown can release USP1 retention and help human skin fibroblasts (HSFs) resist UVA-induced damage. The interactive interface inhibitors of TAGLN/USP1 were screened via virtual docking to search for small molecules that inhibit photoaging. Zerumbone (Zer), a natural product isolated from Zingiber zerumbet (L.) Smith, was screened out. Zer can competitively bind TAGLN to reduce the retention of USP1 in the cytoplasm and the degradation of ZEB1 ubiquitination in UV-induced HSFs. The poor solubility and permeability of Zer can be improved by preparing it as a nanoemulsion, which can effectively prevent skin photoaging caused by UVA in wild-type (WT) mice. Zer cannot effectively resist the photoaging caused by UVA in Tagln(−/−) mice because of target loss. CONCLUSIONS: The present results showed that the interaction of TAGLN and USP1 can promote ZEB1 ubiquitination degradation in UV-induced skin photoaging, and Zer can be used as an interactive interface inhibitor of TAGLN/USP1 to prevent photoaging. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13578-023-01029-z.
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spelling pubmed-101637452023-05-07 Interaction of TAGLN and USP1 promotes ZEB1 ubiquitination degradation in UV-induced skin photoaging Li, Yinan Huang, Xiu Jin, Jing Zhang, Haohao Yang, Kai Han, Jingxia Lv, Ying Sun, Yu Yao, Cheng Lin, Tingting Zhu, Caibin Liu, Huijuan Cell Biosci Research BACKGROUND: Ultraviolet A (UVA) irradiation can lead to skin damage and premature skin aging known as photoaging. This work found that UVA irradiation caused an imbalance between dermal matrix synthesis and degradation through the aberrant upregulation of transgelin (TAGLN) and studied the underlying molecular mechanism. RESULTS: Co-immunoprecipitation and proximal ligation assay results showed that TAGLN can interact with USP1. USP1 can be retained in the cytoplasm by TAGLN in UVA-induced cells, which inhibits the interaction between USP1/zinc finger E-box binding homeobox 1 (ZEB1), promote the ubiquitination degradation of ZEB1, and lead to photoaging. TAGLN knockdown can release USP1 retention and help human skin fibroblasts (HSFs) resist UVA-induced damage. The interactive interface inhibitors of TAGLN/USP1 were screened via virtual docking to search for small molecules that inhibit photoaging. Zerumbone (Zer), a natural product isolated from Zingiber zerumbet (L.) Smith, was screened out. Zer can competitively bind TAGLN to reduce the retention of USP1 in the cytoplasm and the degradation of ZEB1 ubiquitination in UV-induced HSFs. The poor solubility and permeability of Zer can be improved by preparing it as a nanoemulsion, which can effectively prevent skin photoaging caused by UVA in wild-type (WT) mice. Zer cannot effectively resist the photoaging caused by UVA in Tagln(−/−) mice because of target loss. CONCLUSIONS: The present results showed that the interaction of TAGLN and USP1 can promote ZEB1 ubiquitination degradation in UV-induced skin photoaging, and Zer can be used as an interactive interface inhibitor of TAGLN/USP1 to prevent photoaging. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13578-023-01029-z. BioMed Central 2023-05-06 /pmc/articles/PMC10163745/ /pubmed/37149635 http://dx.doi.org/10.1186/s13578-023-01029-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Li, Yinan
Huang, Xiu
Jin, Jing
Zhang, Haohao
Yang, Kai
Han, Jingxia
Lv, Ying
Sun, Yu
Yao, Cheng
Lin, Tingting
Zhu, Caibin
Liu, Huijuan
Interaction of TAGLN and USP1 promotes ZEB1 ubiquitination degradation in UV-induced skin photoaging
title Interaction of TAGLN and USP1 promotes ZEB1 ubiquitination degradation in UV-induced skin photoaging
title_full Interaction of TAGLN and USP1 promotes ZEB1 ubiquitination degradation in UV-induced skin photoaging
title_fullStr Interaction of TAGLN and USP1 promotes ZEB1 ubiquitination degradation in UV-induced skin photoaging
title_full_unstemmed Interaction of TAGLN and USP1 promotes ZEB1 ubiquitination degradation in UV-induced skin photoaging
title_short Interaction of TAGLN and USP1 promotes ZEB1 ubiquitination degradation in UV-induced skin photoaging
title_sort interaction of tagln and usp1 promotes zeb1 ubiquitination degradation in uv-induced skin photoaging
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10163745/
https://www.ncbi.nlm.nih.gov/pubmed/37149635
http://dx.doi.org/10.1186/s13578-023-01029-z
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