A Ribosomal S-6 Kinase–Mediated Signal to C/EBP-β Is Critical for the Development of Liver Fibrosis
Figure 2
Mice expressing the RSK-inhibitory C/EBPβ-Ala217 transgene are resistant to hepatotoxin-induced liver fibrogenesis.
Mice were treated with CCl4 or control mineral oil for 12 or 16 weeks and RT-PCR was performed as described in Materials and Methods. A. RT-PCR for collagen α1 type 1 was induced in C/EBPβ +/+ [wt] mice treated with CCl4 for 12 or 16 weeks (P<0.01). Treatment of these animals after week 8 with the RSK-inhibitory peptide while continuing the exposure to the hepatotoxin, as described in Materials and Methods blocked this increase at week 16 (P<0.05). Collagen α1 type 1 was not increased in livers of C/EBPβ-Ala217 mice at 12 or 16 weeks (P<0.01). B. RT-PCR for α-SMA was induced in C/EBPβ +/+ [wt] mice treated with CCl4 for 12 or 16 weeks (P<0.05). Treatment of these animals after week 8 with the RSK-inhibitory peptide while continuing the exposure to the hepatotoxin, as described in Materials and Methods blocked this increase at week 16 (P<0.05). α-SMA was not increased in livers of C/EBPβ-Ala217 mice at 12 or 16 weeks (P<0.05). C. RT-PCR for TGF-β was induced in C/EBPβ +/+ [wt] mice treated with CCl4 for 12 or 16 weeks (P<0.01). Treatment of these animals after week 8 with the RSK-inhibitory peptide while continuing the exposure to the hepatotoxin, as described in Materials and Methods, blocked this increase at week 16 (P<0.01). TGF-β was not increased in livers of C/EBPβ-Ala217 mice at 12 or 16 weeks (P<0.01).