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

Xiangzhi Li; Yimeng Wang; Xian Wang; Yi Shen; Yawen Yuan; Qingquan He; Shuyi Mao; Cailian Wu; Meijuan Zhou

doi:10.1007/s43630-024-00574-x

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

Photochem Photobiol Sci. 2024 Apr 29. doi: 10.1007/s43630-024-00574-x. Online ahead of print.

Authors

Xiangzhi Li^#^{1

2

3}, Yimeng Wang^#^{1

4}, Xian Wang^#⁵, Yi Shen⁵, Yawen Yuan¹, Qingquan He³, Shuyi Mao⁶, Cailian Wu², Meijuan Zhou⁷

Affiliations

¹ Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China.
² Department of Public Health, School of Medicine, Guangxi University of Science and Technology, Liuzhou, 545000, China.
³ Taizhou Key Laboratory of Minimally Invasive Interventional Therapy & Artificial Intelligence, Taizhou Branch of Zhejiang Cancer Hospital (Taizhou Cancer Hospital), Taizhou, 317502, China.
⁴ Yancheng Center for Disease Control and Prevention, Yancheng, 224000, China.
⁵ Department of Public Health and Management, Youjiang Medical University for Nationalities, Baise, 533000, China.
⁶ Nuclear Medicine Department, The Second Affiliated Hospital of Guangxi University of Science and Technology, Liuzhou, 545006, China.
⁷ Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China. lkzmj@smu.edu.cn.

^# Contributed equally.

PMID: 38684635
DOI: 10.1007/s43630-024-00574-x

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.

Keywords: Apoptosis; Autophagy; EMT; SMAD4; UVB.

Abstract

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