Fig. 8
miR-122 selective inhibitor (NSC5476 (NSC)) abolished the effects of ML141 (ML). hADSCs were induced to Hep-Dif for 28 days with or without ML141 (10 μM) for the indicated time of incubation (D-2/14 or D14/28). Cells were incubated as indicated in Fig. 7 (with H-89, SP, PD, WRT, Wnt5a) and with or without NSC5476 (NSC, 5 μM) 24 h before adding ML141 and maintained in parallel to ML141. a RNAs were collected at D0/14/28 and mRNA levels of hepatocyte nuclear factor (HNF)4α/albumin (ALB)/E-cadherin/miR-122 genes were determined by RT-qPCR: the results are expressed as fold variation relative to D0 (or young at D0) after normalization to GAPDH. b Effects of H-89, SP, PD, WRT, Wnt5a, and NSC on the expression of miR-122 mRNA on the ML(−2/14) treated group. c Effects of Wnt5a, WRT, and NSC on the levels of secreted albumin and released exosomes on the ML141(−2/14) treated group. ¥P < 0.05, aged+ML(14/28) + NSC versus same group without NSC. The results are expressed as fold variation relative to D0 (or young at D0). Results are the mean ± SEM of three independent experiments performed in duplicate realized on 19 (young) and 20 (aged, aged+ML) subjects. φ§*¤P < 0.05, φφ§§**## ¥¥ααP < 0.01, φφφ§§§***P < 0.001. φD14/D28 versus D0, §aged versus young, *aged+ML + NSC versus aged+ML, ¤aged+ML + Wnt5a versus aged+ML, #aged+ML + WRT versus aged+ML, ¥aged+ML + Wnt5a + WRT versus aged+ML, and αaged + ML + Wnt5a + NSC versus aged+ML. PD PD98059, SP SP600125, WRT Wortmannin