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miR-1246-overexpressing exosomes suppress UVB-induced photoaging via regulation of TGF-β/Smad and attenuation of MAPK/AP-1 pathway

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Abstract

Stem cell therapy is widely employed for the treatment of skin diseases, especially in skin rejuvenation. Exosomes derived from stem cells have been demonstrated to possess anti-photoaging effects; however, the precise components within exosomes that are responsible for this effect remain unknown. Previously, miR-1246 was found to be one of the most abundant nucleic acids in adipose-derived stem cells (ADSCs)-derived exosomes. This study examined whether miR-1246 was the major therapeutic agent employed by ADSCs to protect against UVB-induced photoaging. Lentivirus infection was used to obtain miR-1246-overexpressing ADSCs and exosomes. We then determined the anti-photoaging effects of miR-1246-overexpressing exosomes (OE-EX) on both UVB-irradiated human skin fibroblasts (HSFs) and Kunming mice. The results showed that OE-EX could significantly decrease MMP-1 by inhibiting the MAPK/AP-1 signaling pathway. Meanwhile, OE-EX markedly increased procollagen type I secretion by activating the TGF-β/Smad pathway. OE-EX also exhibited an anti-inflammatory effect by preventing the UVB-induced degradation of IκB-α and NF-κB overexpression. Animal experiments demonstrated that OE-EX could reduce UVB-induced wrinkle formation, epidermis thickening, and the loss of collagen fibers reduction in Kunming mice. The combined results suggested that miR-1246 is the key component within ADSCs-derived exosomes that protects against UVB-induced skin photoaging.

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Acknowledgements

This work was supported by grants from the Natural Science Foundation of China (82103755), the Natural Science Foundation of Anhui Province (2108085QH333 and 2008085QH417), the Natural Science Research Project of Anhui Educational Committee (KJ2020A0565), the Innovation program for Returned Overseas Chinese Scholars of Anhui Province (2021LCX027), and the college students’ innovation and entrepreneurship training program of Anhui province (S202110367014).

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Authors and Affiliations

  1. Department of Pharmacy, Bengbu Medical College, 2600 Donghai Avenue, Bengbu, 233030, China

    Wei Gao, Li-min Yuan, Yue Zhang, Fang-zhou Huang, Fei Gao, Jian Li, Feng Xu, Hui Wang & Yu-shuai Wang

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  1. Wei Gao
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  2. Li-min Yuan
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Gao, W., Yuan, Lm., Zhang, Y. et al. miR-1246-overexpressing exosomes suppress UVB-induced photoaging via regulation of TGF-β/Smad and attenuation of MAPK/AP-1 pathway. Photochem Photobiol Sci 22, 135–146 (2023). https://doi.org/10.1007/s43630-022-00304-1

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