HucMSC exosome-delivered 14-3-3ζ alleviates ultraviolet radiation-induced photodamage via SIRT1 pathway modulation.
HucMSC exosome-delivered 14-3-3ζ alleviates ultraviolet radiation-induced photodamage via SIRT1 pathway modulation.
复制标题
DOI：
10.18632/aging.202851
复制
发表时间：
2021-04-21
期刊：
影响因子：
--
通讯作者：
Qian H
中科院分区：
文献类型：
--
作者：
Wu P;Zhang B;Han X;Sun Y;Sun Z;Li L;Zhou X;Jin Q;Fu P;Xu W;Qian H
源自人脐带间充质干细胞的外泌体（hucMSC-ex）是纳米级的膜结合囊泡，据报道其有助于皮肤再生与修复。然而，hucMSC-ex在紫外线（UV）辐射诱导的皮肤光损伤中所起的作用及潜在机制仍不明确。为研究hucMSC-ex在大鼠急性皮肤光损伤模型中的功能，进行了免疫荧光和免疫组化染色、实时荧光定量聚合酶链反应（qRT-PCR）、蛋白质免疫印迹以及基因沉默实验。我们发现，体内皮下注射hucMSC-ex对紫外线辐射诱导的DNA损伤和细胞凋亡具有抗氧化和抗炎作用。进一步研究表明，在体外紫外线辐射诱导的氧化应激条件下，皮肤角质形成细胞（HaCaT）中沉默信息调节因子1（SIRT1）的表达水平呈时间和剂量依赖性下降，而hucMSC-ex处理可逆转这一现象。SIRT1的激活通过抑制氧化应激和促进自噬激活，显著减轻了紫外线和过氧化氢诱导的细胞毒性损伤。我们的研究发现，由hucMSC-ex递送的14-3-3ζ蛋白通过调节SIRT1依赖性抗氧化途径发挥细胞保护功能。总体而言，我们的研究结果表明，hucMSC-ex可能是一种预防或治疗紫外线辐射诱导的皮肤光损伤和衰老的潜在新型制剂。
Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-ex) are nano-sized membrane-bound vesicles that have been reported to facilitate skin regeneration and repair. However, the roles played by hucMSC-ex in ultraviolet (UV) radiation-induced skin photodamage and the underlying mechanisms remain unknown. To investigate the functions of hucMSC-ex in a rat model of acute skin photodamage, immunofluorescence and immunohistochemical staining, quantitative real-time-polymerase chain reaction (qRT-PCR), western blot, and gene silencing assays were performed. We found that the in vivo subcutaneous injection of hucMSC-ex elicited antioxidant and anti-inflammatory effects against UV radiation-induced DNA damage and apoptosis. Further studies showed that the sirtuin 1 (SIRT1) expression level in skin keratinocytes (HaCaT) decreased in a time- and dose-dependent manner under in vitro UV radiation induced-oxidative stress conditions, which could be reversed by treatment with hucMSC-ex. The activation of SIRT1 significantly attenuated UV- and H2O2-induced cytotoxic damage by inhibiting oxidative stress and promoting the activation of autophagy. Our study found that 14-3-3ζ protein, which was delivered by hucMSC-ex, exerted a cytoprotective function via the modulation of a SIRT1-dependent antioxidant pathway. Collectively, our findings indicated that hucMSC-ex might represent a new potential agent for preventing or treating UV radiation-induced skin photodamage and aging.
登录
查看更多内容
影响因子：
23.9
作者：
Caplan AI;Correa D
通讯作者：
Correa D
影响因子：
9
作者：
通讯作者：
--
DOI：
10.1146/annurev.pathol.4.110807.092250
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Haigis MC;Sinclair DA
通讯作者：
Sinclair DA
DOI：
10.1073/pnas.0704421104
发表时间：
2007-06-26
影响因子：
11.1
作者：
Ortiz, Luis A.;DuTreil, Maria;Phinney, Donald G.
通讯作者：
Phinney, Donald G.
影响因子：
--
作者：
Lee JH;Moon JH;Nazim UM;Lee YJ;Seol JW;Eo SK;Lee JH;Park SY
通讯作者：
Park SY