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. 2024 May;23(5):957-972.
doi: 10.1007/s43630-024-00567-w. Epub 2024 Apr 13.

miR-1246-overexpressing exosomes improve UVB-induced photoaging by activating autophagy via suppressing GSK3β

Wei Gao #  1 , Limin Yuan #  1 , Yue Zhang  1 , Fangzhou Huang  1 , Chen Ai  1 , Tianci Lv  1 , Jiale Chen  1 , Hui Wang  1 , Yixin Ling  1 , Yu-Shuai Wang  2
Affiliations

miR-1246-overexpressing exosomes improve UVB-induced photoaging by activating autophagy via suppressing GSK3β

Wei Gao et al. Photochem Photobiol Sci. 2024 May.

Abstract

Stem cell paracrine has shown potential application in skin wound repair and photoaging treatment. Our previous study demonstrated that miR-1246-overexpressing Exosomes (OE-EXs) isolated from adipose-derived stem cells (ADSCs) showed superior photo-protecting effects on UVB-induced photoaging than that of the vector, however, the underlying mechanism was unclear. The simultaneous bioinformatics analysis indicated that miR-1246 showed potential binding sites with GSK3β which acted as a negative regulator for autophagy. This study was aimed to explore whether OE-EXs ameliorate skin photoaging by activating autophagy via targeting GSK3β. The results demonstrated that OE-EXs significantly decreased GSK3β expression, enhanced autophagy flux and autophagy-related proteins like LC3II, while suppressed p62 expression. Meanwhile, OE-EXs markedly reversed the levels of intracellular ROS, MMP-1, procollagen type I and DNA damage in human skin fibroblasts caused by UVB irradiation, but the ameliorating effects were significantly inhibited when 3-Methyladenine (3-MA) was introduced to block the autophagy pathway. Further, OE-EXs could reverse UVB-induced wrinkles, epidermal hyperplasia, and collagen fibers reduction in Kunming mice, nevertheless, the therapeutical effects of OE-EXs were attenuated when it was combinative treated with 3-MA. In conclusion, OE-EXs could cure UVB induced skin photoaging by activating autophagy via targeting GSK3β.

Keywords: Autophagy; Exosomes; GSK3β; Photoaging; miR-1246.

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