Nacka-Aleksić Mirjana, Pirković Andrea, Vilotić Aleksandra, Kosanović Maja, Dekanski Dragana, Legner Janko, Jovanović Krivokuća Milica
University of Belgrade, Institute for the Application of Nuclear Energy (INEP), Department for Biology of Reproduction, Banatska 31b, 11080 Zemun, Serbia.
University of Belgrade, Institute for the Application of Nuclear Energy (INEP), Department for Immunology and Immunoparasitology, Banatska 31b, 11080 Zemun, Serbia.
Life (Basel). 2025 Jun 5;15(6):918. doi: 10.3390/life15060918.
Keratinocyte stress, caused by various intrinsic and extrinsic factors, contributes to the overall aging process. D-galactose-induced metabolic/oxidative stress is a commonly used model for studying premature aging. Due to their rich composition of bioactive molecules that influence critical pathways in cellular aging and rejuvenation, placental derivatives have a well-established history in anti-aging skincare and therapy. However, trophoblast-derived extracellular vesicle (TEV) effects on D-galactose-induced premature aging in keratinocytes have not been investigated yet. TEV pretreatment for 24 h enhanced cellular resilience against D-galactose-induced stress, judging by the downregulated expression of senescence- and stress-associated markers (p19 and p21, HIF-1α, mTOR), and reduced production of reactive oxygen species and DNA damage. Additionally, TEV pretreatment enhanced keratinocyte proliferation and integrin-β1 subunit expression upon D-galactose exposure, most likely contributing to more efficient wound closure. In conclusion, this study underscores the potential of TEVs to modify expression of stress- and senescence-related proteins in keratinocytes and improve their wound healing properties. Their regenerative and protective characteristics position TEVs as promising candidates for developing innovative procedures to address skin conditions related to premature aging.
由各种内在和外在因素引起的角质形成细胞应激，会导致整体衰老过程。D-半乳糖诱导的代谢/氧化应激是研究早衰的常用模型。由于胎盘衍生物富含影响细胞衰老和年轻化关键途径的生物活性分子，因此在抗衰老护肤和治疗方面有着悠久的历史。然而，滋养层来源的细胞外囊泡（TEV）对D-半乳糖诱导的角质形成细胞早衰的影响尚未得到研究。通过衰老和应激相关标志物（p19和p21、HIF-1α、mTOR）表达下调以及活性氧产生减少和DNA损伤减轻判断，TEV预处理24小时可增强细胞对D-半乳糖诱导应激的恢复力。此外，TEV预处理可增强D-半乳糖暴露后角质形成细胞的增殖和整合素-β1亚基表达，这很可能有助于更有效地闭合伤口。总之，本研究强调了TEV改变角质形成细胞中应激和衰老相关蛋白表达以及改善其伤口愈合特性的潜力。它们的再生和保护特性使TEV成为开发解决与早衰相关皮肤状况的创新方法的有希望的候选者。
