Fig. 8

MSC-EV rescues HDFs photoaging by downregulating NOTCH signaling pathway. a Venn diagram showing the overlapped genes between photoaging (UVB/Control) and Treatment (EV/UVB) based on data from RNA-seq. Rev-photoaging-DEGs were defined as subsets of overlapped DEGs that were changed in the opposite direction in photoaging and treatment. b Representative GO terms of Rev-photoaging DEGs for Biological Process (green), Cellular Component (orange), and Molecular Function (blue) were shown. c Heatmaps showing the expression profile of genes in response to UVB and EV treatment in Notch signaling. d Quantitation of different mRNA levels of Hes1, Tle1, Lfng, Dll1, and HeyL. e Western blot analysis showing expression of NOTCH1, NICD1, HES1, SIRT1, P16, P21, P53 and GAPDH after EV treatment. f Western blot analysis showing expression of NOTCH1, NICD1, HES1, SIRT1, P16, P21, P53 and GAPDH after TIMP1 treatment. g Representative immunofluorescence staining images of positive cells of HES1 in nude mice dorsal skin injected PBS, AMSC-EV, or HUMSC-EV (top, scale bar, 30 μm; bottom, scale bar, 10 μm). h Representative immunofluorescence staining images of SA-β-gal (scale bar, 100 μm), ROS (green), and γ-H2Ax (red) (scale bar, 30 μm). i Luciferase-reporter assays of HES1 transcriptional activity in HDFs after UVB, FM (culture medium), EV, TIMP1, GI254023X, and VPA treatment. n = 3, **P < 0.01, ***P < 0.001, ****P < 0.0001. j Schematic of the role of EV in mediating UVB-induced photoaging of Notch signaling and cellular senescence. (Created with BioRender.com)