Cross-talk between IFN-α and TGF-β1 signaling pathways in preneoplastic rat liver

• Published in: Growth factors (Chur, Switzerland) Switzerland), 2009-01, Vol.27 (1), p.1-11
• Main Authors: De Luján Alvarez, María, Quiroga, Ariel D., Parody, Juan P., Ronco, María Teresa, Francés, Daniel E., Carnovale, Cristina E., Carrillo, María Cristina
• Format: Article
• Language: English
• Subjects: p300; Preneoplastic rat hepatocytes; Smad2/3; Smad7; Stat1
• ISSN: 0897-7194; 1029-2292
• DOI: 10.1080/08977190802547357

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-β 1 production and secretion in hepatocytes from preneoplastic rat livers. Here, the interaction between IFN-α/TGF-β 1 pathways was explored. We observed a positive cross-talk between IFN-α and TGF-β 1 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-β 1 and IFN-α signals. Interestingly, we reported the novel finding that the autocrine TGF-β 1 up-regulates TGF-βRII at protein and mRNA levels. In conclusion, the intracellular signals triggered by IFN-α2b and by autocrine TGF-β 1 are integrated at the nuclear level, where activated Stat1 and Smad2/3 are capable of interact with p300, present in no restrictive cellular amounts.