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

被引:12
作者
Alvarez, Maria De Lujan [1 ]
Quiroga, Ariel D. [1 ]
Parody, Juan P. [1 ]
Ronco, Maria Teresa [1 ]
Frances, Daniel E. [1 ]
Carnovale, Cristina E. [1 ]
Carrillo, Maria Cristina [1 ]
机构
[1] Univ Nacl Rosario, Fac Ciencias Bioquim & Farmaceut, Inst Fisiol Expt IFISE, CONICET, RA-2000 Rosario, Santa Fe, Argentina
关键词
Preneoplastic rat hepatocytes; p300; Smad7; Stat1; Smad2/3; GROWTH-FACTOR-BETA; TGF-BETA; INTERFERON-ALPHA; STELLATE CELLS; I RECEPTOR; EXPRESSION; SMAD7; GAMMA; FIBROSIS; CARCINOGENESIS;
D O I
10.1080/08977190802547357
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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-alpha 2b 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-a signals. Interestingly, we reported the novel finding that the autocrine TGF-beta(1) up-regulates TGF-beta RII at protein and mRNA levels. In conclusion, the intracellular signals triggered by IFN-alpha 2b 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.
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页码:1 / 11
页数:11
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