Cross-talk between IFN-alpha and TGF-beta1 signaling pathways in preneoplastic rat liver.
Interferon-gamma/transforming growth factor-beta (IFN-gamma/TGF-beta) pathways have opposite effects on diverse cellular functions. However, little is known about interactions between IFN-alpha/TGF-beta. In previous studies, we showed that IFN-alpha2b increases TGF-beta(1) production and secretion in hepatocytes from preneoplastic rat livers. Here, the interaction between IFN-alpha/TGF-beta(1) pathways was explored. We observed a positive cross-talk between IFN-alpha and TGF-beta(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-beta(1) and IFN-alpha signals. Interestingly, we reported the novel finding that the autocrine TGF-beta(1) up-regulates TGF-betaRII at protein and mRNA levels. In conclusion, the intracellular signals triggered by IFN-alpha2b and by autocrine TGF-beta(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.
Alvarez
María De Luján
Mde L
Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Facultad de Ciencias Bioquimicas y Farmaceuticas, Instituto de Fisiologia Experimental, Universidad Nacional de Rosario, Rosario, Argentina.
Quiroga
Ariel D
AD
Parody
Juan P
JP
Ronco
María Teresa
MT
Francés
Daniel E
DE
Carnovale
Cristina E
CE
Carrillo
María Cristina
MC
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D050881:E1A-Associated p300 Protein / Q000378:metabolism; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000378:metabolism*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology; D008114:Liver Neoplasms, Experimental / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D011230:Precancerous Conditions / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; D051899:Smad2 Protein; C497784:Smad2 protein, rat; D051900:Smad3 Protein; C497787:Smad3 protein, rat; C494081:Stat1 protein, rat; D053773:Transforming Growth Factor beta1; D050881:E1A-Associated p300 Protein; C494362:Ep300 protein, rat