2. Academic Validation
  3. TIMP3 deficiency accelerates UVB-induced HaCaT cell senescence by regulating ferroptosis

TIMP3 deficiency accelerates UVB-induced HaCaT cell senescence by regulating ferroptosis

  • Photochem Photobiol Sci. 2025 Mar 21. doi: 10.1007/s43630-025-00701-2.
Yan Teng 1,  Junjia He 1,  Yeyu Shen 1,  Jie Chen 2,  Ye Qian 3,  Youming Huang 1,  Xiaohua Tao 1,  Danfeng Xu 4,  Yibin Fan 5
Affiliations

Affiliations

  • 1 Center for Plastic and Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital of Hangzhou Medical College, Hangzhou, 310014, Zhejiang, People's Republic of China.
  • 2 Zhuji Sixth People's Hospital, Zhuji, Zhejiang, People's Republic of China.
  • 3 Department of Gastroenterology, Chun'an County First People's Hospital (Zhejiang Provincial People's Hospital, Chun'an Branch), Hangzhou, Zhejiang, People's Republic of China.
  • 4 Center for Plastic and Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital of Hangzhou Medical College, Hangzhou, 310014, Zhejiang, People's Republic of China. 3100102508@zju.edu.cn.
  • 5 Center for Plastic and Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital of Hangzhou Medical College, Hangzhou, 310014, Zhejiang, People's Republic of China. fanyibin@hmc.edu.cn.
PMID: 40117061 DOI: 10.1007/s43630-025-00701-2
Abstract

Prolonged exposure to ultraviolet B (UVB) light leads to the accumulation of Reactive Oxygen Species (ROS), a key contributor to skin aging. Previous studies have demonstrated that UVB exposure results in a deficiency in the expression of TIMP3 in keratinocytes. The objective of this study was to investigate the specific role of TIMP3 in keratinocytes. UVB-treated HaCaT cells were utilized to establish a cellular photoaging model. We found that UVB significantly increased levels of ROS, promoted senescence and Ferroptosis, and inhibited the expression of TIMP3 in HaCaT. This inhibition was notably alleviated by Fer-1, a Ferroptosis inhibitor. In addition, the knockdown of TIMP3 in HaCaT enhanced senescence by inducing the Ferroptosis. Mechanistically, UVB exposure also led to a decrease in the expression of KLF4, a transcription factor that regulated TIMP3 expression. Futhermore, UVB-induced reduced expression of KLF4 and TIMP3 in vivo. Our results suggest that deletion of the KLF4/TIMP3 axis promotes HaCaT cell senescence by facilitating the progression of Ferroptosis. TIMP3 may serve as an effective therapeutic target for preventing skin photoaging.

Keywords

Ferroptosis; KLF4; ROS; Skin senescence; TIMP3.

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