HucMSC外泌体携载14-3-3ζ调控E2F1/SIRT1延缓皮肤光老化的作用及机制

干细胞抗衰老是当今生命科学中的研究热点，而作为干细胞旁分泌中的重要组分外泌体在光诱导皮肤衰老中的作用机制尚未明确。我们前期研究显示人脐带间充质干细胞源外泌体（hucMSC-ex）能缓解皮肤光损伤，其中富含的14-3-3ζ蛋白可明显促进氧化应激状态下皮肤细胞中去乙酰化酶1（SIRT1）的表达。基于此，本研究旨在探讨hucMSC-ex携载14-3-3ζ调控转录因子E2F1/SIRT1延缓皮肤光老化的作用及机制。本研究拟采用三维细胞培养方法制备丰富的hucMSC-ex，构建皮肤光老化体内外干预模型，通过基因转染获得敲减和过表达14-3-3ζ的hucMSC-ex，明确hucMSC-ex携载14-3-3ζ对皮肤光老化的防御作用；通过RNA干扰和免疫共沉淀等细胞分子技术，揭示14-3-3ζ调控E2F1泛素化促进SIRT1信号通路的分子机制，为预防皮肤光老化提供新策略，为医学美容抗衰研究提供理论依据。

Stem cell therapy for anti-aging is a hot topic in life science, but the mechanism of exosomes, an important paracrine factor of stem cells, in photoinduced skin aging is not clear. Our previous studies have shown that human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-exs) can alleviate skin photodamage, and the protein 14-3-3ζ rich in hucMSC-exs can significantly promote sirtuin 1 (SIRT1) expression in skin cells under oxidative stress. Based on these, this study will investigate the effect and mechanism of hucMSC-exs carrying 14-3-3ζ regulating the transcription factor E2F1 and SIRT1 on skin photoaging. In this study, we will use three-dimensional cell culture systems to prepare abundant hucMSC-exs for establishing in vitro and in vivo intervention models of skin photoaging, and through knock-down and over-expression of 14-3-3ζ, clarify the protective effect of hucMSC-exs carrying 14-3-3ζ on skin photoaging. Furthermore, we will study the molecular mechanism of 14-3-3ζ regulating E2F1 ubiquitination and promoting SIRT1 signal pathway through RNAi, co-immunoprecipitation, etc. This study will provide a novel strategy for preventing skin photoaging and theoretical bases for anti-aging and medical cosmetology.