Research Paper Volume 15, Issue 6 pp 1859—1877

P53/miR-34a/SIRT1 positive feedback loop regulates the termination of liver regeneration

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Figure 4. T-β-MCA enhanced the proapoptotic effect of the P53-activated P53/miR-34a/SIRT1 positive feedback loop by suppressing the FXR/SHP signaling pathway in vitro. (A) Heatmap of changed Bas during LR. (B) Percentage of the top 3 BAs at the indicated time points after PH. (C) Concentration of T-β-MCA at the indicated time points after PH. (D) TUNEL staining of primary hepatocytes after knock-in of P53 with/without administration of T-β-MCA and GW4064(magnification: × 400, Scale bars represent 50 μm). (E) Quantification of TUNEL-positive cells after knock-in of P53 with/without administration of T-β-MCA and GW4064. (F) Quantification of hepatic miR-34a expression in mouse primary hepatocytes after knock-in of P53 with/without administration of T-β-MCA and GW4064 by qPCR. (G) Protein expression of P53/miR-34a/SIRT1 positive feedback loop genes and FXR/SHP signaling after knock-in of P53 with/without administration of T-β-MCA and GW4064. Cells were pretreated with/without 100 μM T-β-MCA or 1 μM GW4064 for 12 h. (H) Quantification of P53, Ace-P53, SIRT1, P21, FXR, and SHP protein expression by WB. (ns: p>0.05; *, p<0.05; **, p<0.01; ***, p<0.001).