Temporal Regulation of UVA-Induced Ferroptosis-Associated Injury in Keratinocytes
- 1Key Laboratory of Molecular Epidemiology of Hunan Province, School of Public Health, Health Science Center, Hunan Normal University, Changsha 410013, China
Abstract
Ferroptosis contributes to ultraviolet (UV)-induced epidermal injury, but whether circadian state modifies keratinocyte susceptibility remains unclear. We integrated human epidermal transcriptomic analyses with functional experiments in HaCaT keratinocytes to compare UVA- and UVB-induced ferroptosis-associated responses and assess their temporal regulation. Both wavelengths reduced cell viability and increased reactive oxygen species, lipid peroxidation, and intracellular Fe2+ accumulation; ferrostatin-1 provided partial protection. UVB reduced xCT and GPX4 and showed a proteasome-sensitive component of GPX4 loss, whereas UVA predominantly reduced GPX4 without detectably altering xCT. Human epidermal transcriptomes showed heterogeneous cross-sectional associations among circadian, oxidative-stress, and ferroptosis-related genes, while longitudinal profiles revealed positive temporal coupling between NR1D1-associated signals and GPX4. In synchronized HaCaT cells, ARNTL and NR1D1 displayed 24 h rhythmicity, whereas GPX4 and SLC7A11 did not meet the prespecified rhythmicity criterion. Nevertheless, UVA-induced cytotoxicity, oxidative stress, lipid peroxidation, and GPX4 loss varied across post-synchronization time points and were greatest at 24 h. SR8278 partially preserved GPX4 abundance and attenuated UVA-induced loss of viability, reactive oxygen species accumulation, and lipid peroxidation, without significantly affecting Fe2+ accumulation. These findings associate circadian state with temporal variation in UVA-induced ferroptosis susceptibility and implicate the broader clock-redox system rather than rhythmic expression of individual ferroptosis effectors.
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BibTeX
@article{dong2026temporal,
title = {{Temporal Regulation of UVA-Induced Ferroptosis-Associated Injury in Keratinocytes}},
author = {Ren Dong and Xiang Li and Ping Wang and Qianxian Yin and Zirun Wang and Ying Xie},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27208947},
url = {https://www.mdpi.com/1422-0067/27/20/8947},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Temporal Regulation of UVA-Induced Ferroptosis-Associated Injury in Keratinocytes
AU - Ren Dong
AU - Xiang Li
AU - Ping Wang
AU - Qianxian Yin
AU - Zirun Wang
AU - Ying Xie
PY - 2026
DA - 2026/10/09
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27208947
UR - https://www.mdpi.com/1422-0067/27/20/8947
AB - Ferroptosis contributes to ultraviolet (UV)-induced epidermal injury, but whether circadian state modifies keratinocyte susceptibility remains unclear. We integrated human epidermal transcriptomic analyses with functional experiments in HaCaT keratinocytes to compare UVA- and UVB-induced ferroptosis-associated responses and assess their temporal regulation. Both wavelengths reduced cell viability and increased reactive oxygen species, lipid peroxidation, and intracellular Fe2+ accumulation; ferrostatin-1 provided partial protection. UVB reduced xCT and GPX4 and showed a proteasome-sensitive component of GPX4 loss, whereas UVA predominantly reduced GPX4 without detectably altering xCT. Human epidermal transcriptomes showed heterogeneous cross-sectional associations among circadian, oxidative-stress, and ferroptosis-related genes, while longitudinal profiles revealed positive temporal coupling between NR1D1-associated signals and GPX4. In synchronized HaCaT cells, ARNTL and NR1D1 displayed 24 h rhythmicity, whereas GPX4 and SLC7A11 did not meet the prespecified rhythmicity criterion. Nevertheless, UVA-induced cytotoxicity, oxidative stress, lipid peroxidation, and GPX4 loss varied across post-synchronization time points and were greatest at 24 h. SR8278 partially preserved GPX4 abundance and attenuated UVA-induced loss of viability, reactive oxygen species accumulation, and lipid peroxidation, without significantly affecting Fe2+ accumulation. These findings associate circadian state with temporal variation in UVA-induced ferroptosis susceptibility and implicate the broader clock-redox system rather than rhythmic expression of individual ferroptosis effectors.
SN - 1422-0067
ER -