Open AccessHucMSC exosome-delivered 14-3-3ζ alleviates ultraviolet radiation-induced photodamage via SIRT1 pathway modulation
Author(s) -
Peipei Wu,
Bin Zhang,
Xinye Han,
Yaoxiang Sun,
Zixuan Sun,
Linli Li,
Xinru Zhou,
Qian Jin,
Peiwen Fu,
Wenrong Xu,
Hui Qian
Publication year - 2021
Publication title -
aging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.473
H-Index - 90
ISSN - 1945-4589
DOI - 10.18632/aging.202851
Subject(s) - exosome , ultraviolet , ultraviolet radiation , modulation (music) , radiation , microbiology and biotechnology , chemistry , optoelectronics , materials science , optics , microvesicles , physics , biology , biochemistry , microrna , gene , acoustics , radiochemistry
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 H 2 O 2 -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.