Cross-talk between IFN-a and TGF-b1 signaling pathways in preneoplastic rat liver

QUIROGA, ARIEL DARIO; ALVAREZ, MARIA DE LUJAN; PARODY, JUAN PABLO; RONCO, MARIA TERESA; FRANCES, DANIEL ELEAZAR ANTONIO; CARNOVALE, CRISTINA ESTER; CARRILLO, MARÍA CRISTINA

GROWTH FACTORS

TAYLOR & FRANCIS LTD

Año: 2008 p. 1 - 11

0897-7194

Interferon-g/transforming growth factor-b (IFN-g/TGF-b) pathways have opposite effects on diverse cellular functions. However, little is known about interactions between IFN-a/TGF-b. In previous studies, we showed that IFN-a2b increases TGF-b1 production and secretion in hepatocytes from preneoplastic rat livers. Here, the interaction between IFN-a/TGF-b1 pathways was explored. We observed a positive cross-talk between IFN-a and TGF-b1 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-b1 and IFN-a signals. Interestingly, we reported the novel finding that the autocrine TGF-b1 up-regulates TGF-bRII at protein and mRNA levels. In conclusion, the intracellular signals triggered by IFN-a2b and by autocrine TGF-b1 are integrated at the nuclear level, where activated Stat1 and Smad2/3 are capable of interact with p300, present in no restrictive cellular amounts.