@article{GAO2024, 
author = {Yuanyuan GAO and Hengguang ZHAO and Guihong YANG and Xia LEI},
title = {Protective role of DDIT4-mediated autophagy in dermal papilla cells after oxidative stress injury},
year = {2024},
journal = {Journal of Army Medical University},
volume = {46},
number = {21},
pages = {2397-2406},
keywords = {oxidative stress, autophagy, DNA damage induced transcription factor 4, dermal papilla cells},
url = {https://www.sciopen.com/article/10.16016/j.2097-0927.202406063},
doi = {10.16016/j.2097-0927.202406063},
abstract = {ObjectiveTo explore the protective role of DNA damage induced transcription factor 4 (DDIT4) in oxidative stress injury in dermal papilla cells and its underlying mechanisms.MethodsDermal papilla cells were exposed to UVA and H2O2 to establish cellular model of oxidative stress. CCK-8 assay was used to detect cell viability under different treatment conditions, and the production of intracellular reactive oxygen species (ROS) was detected using 2′, 7′-dichlorofluorescein diacetate (DCFH-DA). Autophagic vesicles were observed with electron microscopy. Western blotting was employed to measure the expression of DDIT4 and autophagy-related molecules, including microtubule-associated protein 1 light chain 3 (LC3), ubiquitin-binding protein (P62), mammalian target of rapamycin (mTOR), and p-mTOR.ResultsUVA and H2O2 resulted in more production of ROS (P<0.05) and decreased viability of dermal papilla cells (P<0.05). DDIT4 expression was increased in dermal papilla cells under oxidative stress (P<0.05), and the antioxidant N-acetyl-L-cysteine (NAC) could effectively inhibit this effect (P<0.05). After treatment with UVA or H2O2, cell autophagy was enhanced in dermal papilla cells, characterized by an increase in the number of autophagosomes and an increased LC3Ⅱ/Ⅰ ratio (P<0.05), a decrease in P62 expression (P<0.05), and 3-methyladenine (3-MA) blocking autophagy led to further reduced cell viability (P<0.05) and increased intracellular ROS production (P<0.05). Conversely, rapamycin (RAPA) increased autophagy level and improved the viability of dermal papilla cells under oxidative conditions (P<0.05), and reduced the generation of intracellular ROS (P<0.05). Additionally, down-regulation of DDIT4 weakened autophagy in dermal papilla cells under oxidative stress, reduced LC3Ⅱ/Ⅰ (P<0.05), increased p-mTOR/mTOR and P62 (P<0.05), inhibited cell viability (P<0.05), and enhanced intracellular ROS production (P<0.05).ConclusionDDIT4 may alleviate oxidative stress injury in dermal papilla cells through autophagy.}
}