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Downregulation of SMAD4 protects HaCaT cells against UVB-induced damage and oxidative stress through the activation of EMT

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Abstract

As a member of the SMAD family, SMAD4 plays a crucial role in several cellular biological processes. However, its function in UVB radiation-induced keratinocyte damage is not yet clarified. Our study aims to provide mechanistic insight for the development of future UVB protective therapies and therapeutics involving SMAD4. HaCaT cells were treated with UVB, and the dose dependence and time dependence of UVB were measured. The cell function of UVB-treated HaCaT cells and the activity of epithelial-mesenchymal transition (EMT) after overexpression or silencing of SMAD4 was observed by flow cytometry, quantitative reverse transcription PCR (qRT-PCR) and Western Blots (WB). We found that a significant decrease in SMAD4 was observed in HaCaT cells induced by UVB. Our data confirm SMAD4 as a direct downstream target of miR-664. The down-regulation of SMAD4 preserved the viability of the UVB-treated HaCaT cells by inhibiting autophagy or apoptosis. Furthermore, the silencing of SMAD4 activated the EMT process in UVB-treated HaCaT cells. Down-regulation of SMAD4 plays a protective role in UVB-treated HaCaT cells via the activation of EMT.

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Funding

This work was supported by the National Natural Science Foundation of China (31971167 and 82273582), the Science and Technology Program of Traditional Chinese Medicine of Zhejiang Province(2024ZL1261), the Science and Technology Plan Projects of Liuzhou (2022CAC0229), the Self-Funded Scientific Research Project of Guangxi Health and Family Planning Commission (Z20211580) and College Students' Innovative Entrepreneurial Training Plan Program (202110594024).

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  1. Xiangzhi Li, Yimeng Wang and Xian Wang contributed equally to this paper.

Authors and Affiliations

  1. Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China

    Xiangzhi Li, Yimeng Wang, Yawen Yuan & Meijuan Zhou

  2. Department of Public Health, School of Medicine, Guangxi University of Science and Technology, Liuzhou, 545000, China

    Xiangzhi Li & Cailian Wu

  3. Taizhou Key Laboratory of Minimally Invasive Interventional Therapy & Artificial Intelligence, Taizhou Branch of Zhejiang Cancer Hospital (Taizhou Cancer Hospital), Taizhou, 317502, China

    Xiangzhi Li & Qingquan He

  4. Yancheng Center for Disease Control and Prevention, Yancheng, 224000, China

    Yimeng Wang

  5. Department of Public Health and Management, Youjiang Medical University for Nationalities, Baise, 533000, China

    Xian Wang & Yi Shen

  6. Nuclear Medicine Department, The Second Affiliated Hospital of Guangxi University of Science and Technology, Liuzhou, 545006, China

    Shuyi Mao

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  1. Xiangzhi Li
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Meijuan Zhou: Conceptualization, Methodology, Writing-original draft. Xiangzhi Li and Yimeng Wang: Conceptualization, Methodology, Writing-original draft and Visualization. Xian Wang, Qingquan He and Cailian Wu: Conceptualization, Methodology, Writing-initial draft. Yi Shen, Yawen Yuan and Shuyi Mao: Methodology, Software, Investigation.

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Li, X., Wang, Y., Wang, X. et al. Downregulation of SMAD4 protects HaCaT cells against UVB-induced damage and oxidative stress through the activation of EMT. Photochem Photobiol Sci (2024). https://doi.org/10.1007/s43630-024-00574-x

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