Cross-talk between IFN-α and TGF-β1 signaling pathways in preneoplastic rat liverContributed equally to this work

Interferon-γ/transforming growth factor-β (IFN-γ/TGF-β) pathways have opposite effects on diverse cellular functions. However, little is known about interactions between IFN-α/TGF-β. In previous studies, we showed that IFN-α2b increases TGF-β1 production and secretion in hepatocytes from preneoplastic rat livers. Here, the interaction between IFN-α/TGF-β1 pathways was explored. We observed a positive cross-talk between IFN-α and TGF-β1 signaling, with activation of both pathways. p300 protein levels in hepatocytes from preneoplastic livers were enough to interact with both activated Stat1 and Smad2/3. Besides, Smad7 was not directly related with TGF-β1 and IFN-α signals. Interestingly, we reported the novel finding that the autocrine TGF-β1 up-regulates TGF-βRII at protein and mRNA levels. In conclusion, the intracellular signals triggered by IFN-α2b and by autocrine TGF-β1 are integrated at the nuclear level, where activated Stat1 and Smad2/3 are capable of interact with p300, present in no restrictive cellular amounts.