EGFR mediates hepatocyte proliferation and liver regeneration. (IMAGE)
Caption
(A) WB revealed that EGFR was activated by recombinant proteins of AREG (50 ng/mL) and EREG (20 ng/mL) in LO2 cells. (B) The MTT assay at 24 and 48 h suggested that gefitinib could block the proliferation of hepatocytes induced by AREG (50 ng/mL) and EREG (20 ng/mL) in LO2 cells (the results of statistical analysis were obtained by comparing with the 0 μM Gef group, respectively). (C) WB demonstrated that ERK1/2 was activated by recombinant proteins of AREG (50 ng/mL) and EREG (20 ng/mL) in LO2 cells. (D) The MTT assay confirmed that the proliferation of LO2 cells induced by AREG and EREG was partially reversed by ravoxertinib (ERK1/2 inhibitor) (the results of statistical analysis were obtained by comparing with the AREG+DMSO group). (E) WB indicated that activation of ERK1/2 induced by recombinant proteins of AREG and EREG were not inhibited by gefitinib. (F) Schematic diagram of the proposed mechanism by which AREG and EREG promote hepatocyte proliferation and partial epithelial–mesenchymal transition. (G) Immunofluorescence analysis revealed higher expression of EGFR in hepatocytes of rat tissues in zone 1 and zone 2 than in zone 3. (H) Schematic diagram of the application scheme of gefitinib and vehicle. (I) The future liver weight (FLW) to body weight (BW) ratio was calculated after PVL 48 h in the vehicle and gefitinib groups. (J, K) Immunofluorescence staining of Ki67 and PCNA in liver sections from DMSO (n = 3) and gefitinib (n = 3) rats at 48 h after PVL. Ki67-and PCNA-positive hepatocytes were counted in three PV-CV fields, and the average count of these three fields was set as the Ki67-and PCNA-positive cell number of one rat. (L) Gefitinib inhibited the proliferation of S5–S7 hepatocytes at 48 h after PVL and delayed liver regeneration. ∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001, ∗∗∗∗P < 0.0001; two-tailed Student's t-tests.
Credit
Genes & Diseases
Usage Restrictions
Credit must be given to the creator. Only noncommercial uses of the work are permitted. No derivatives or adaptations of the work are permitted.
License
CC BY-NC-ND