Research Paper Volume 13, Issue 8 pp 11542—11563
HucMSC exosome-delivered 14-3-3ζ alleviates ultraviolet radiation-induced photodamage via SIRT1 pathway modulation
- 1 Key Laboratory of Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, People’s Republic of China
- 2 Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, People’s Republic of China
- 3 Department of Laboratory Medicine, Affiliated Hospital of Jining Medical University, Jining 272000, Shandong, People’s Republic of China
Received: June 29, 2020 Accepted: February 1, 2021 Published: April 21, 2021https://doi.org/10.18632/aging.202851
How to Cite
Copyright: © 2021 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.