Ru Zha, Wu Yu, Qu Qian, Miao Yong, Zhu Lei, Hu Zhiqi
Department of Plastic and Aesthetic Surgery, Nanfang Hospital of Southern Medical University, No 1838, Guangzhou North Road, Guangzhou, 510515, China.
Department of Dermatology and Aesthetic Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, No 600, Tianhe Road, Guangzhou, 510630, China.
Sci Rep. 2025 Jul 9;15(1):24789. doi: 10.1038/s41598-025-08968-2.
Skin photoaging results primarily from chronic ultraviolet (UV) exposure, which disrupts dermal homeostasis and promotes cellular senescence. Dermal papilla cell-conditioned medium (DPC-CM) has emerged as a promising cell-free approach for skin rejuvenation. This study aimed to explore the anti-photoaging effects of DPC-CM and its potential regulation of ferroptosis. Mouse dermal papilla cells and skin fibroblasts were isolated and characterized. A photoaging model was established using UVA-irradiated fibroblasts, followed by treatment with DPC-CM at two concentrations, the ferroptosis inhibitor ferrostatin-1 (FER-1), or retinoic acid. UVA exposure led to reduced cell viability, impaired migration, increased senescence, elevated iron and reactive oxygen species levels, decreased glutathione, and altered expression of ferroptosis-related markers including nuclear factor erythroid 2-related factor 2 (NRF2), glutathione peroxidase 4 (GPX4), and solute carrier family 7 member 11 (SLC7A11). These changes were partially reversed by DPC-CM and FER-1. Proteomic analysis revealed that proteins in both dermal papilla cells and DPC-CM are associated with ferroptosis pathways. In vivo, DPC-CM significantly attenuated UVA-induced dermal aging. Collectively, these findings demonstrate that DPC-CM protects against photoaging by modulating ferroptosis, supporting its therapeutic potential in oxidative stress-related skin disorders.
皮肤光老化主要源于长期紫外线（UV）照射，这会破坏真皮内稳态并促进细胞衰老。真皮乳头细胞条件培养基（DPC-CM）已成为一种有前景的非细胞皮肤年轻化方法。本研究旨在探讨DPC-CM的抗光老化作用及其对铁死亡的潜在调节作用。分离并鉴定了小鼠真皮乳头细胞和皮肤成纤维细胞。使用紫外线A（UVA）照射的成纤维细胞建立光老化模型，然后用两种浓度的DPC-CM、铁死亡抑制剂铁抑素-1（FER-1）或视黄酸进行处理。UVA照射导致细胞活力降低、迁移受损、衰老增加、铁和活性氧水平升高、谷胱甘肽减少以及铁死亡相关标志物的表达改变，包括核因子红细胞2相关因子2（NRF2）、谷胱甘肽过氧化物酶4（GPX4）和溶质载体家族7成员11（SLC7A11）。DPC-CM和FER-1部分逆转了这些变化。蛋白质组学分析表明，真皮乳头细胞和DPC-CM中的蛋白质都与铁死亡途径相关。在体内，DPC-CM显著减轻了UVA诱导的皮肤老化。总的来说，这些发现表明DPC-CM通过调节铁死亡来预防光老化，支持其在氧化应激相关皮肤疾病中的治疗潜力。
