RESUMEN
The heart failure (HF) diseaseasome is marked by substantial alteration in networked signaling pathways. Reductionist paradigm HF investigative approaches have focused on the regulation of a single pathway or single pathway components. In support of a more comprehensive systems biology investigative paradigm, rapidly evolving experimental evidence supports extensive regulatory cross-talk between the TGF-superfamily, Wnt/-catenin and Hippo signaling systems in homeostasis, myocardial development and a variety of non-myocardial diseases. After reviewing the basic components and integrated regulation of each of these three pathways, we review landmark studies in diverse conditions and diseases highlighting the likely critical importance of regulatory cross-talk between these three pathways in the HF.
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Objective To investigate the interaction between HBx protein and ?-catenin for exploring molecular mechanism in HBV-associated hepatocellular carcinoma.Methods Iimmunocytochemistry and Luciferase Assay were used to detect the endocellular location and transcriptional activity of ?-catenin in normal liver cell line L02 infected by Ad-HBx.Results Immunocytochemistry: there was markedly increased expression of ?-catenin in cytoplasm and nucleus.Luciferase Assay: Ad-HBx led to a significant increase of TCF-4-dependent transcription,the TOP count of Ad-GFP and Ad-HBx-GFP was 1.4 fold and 11 fold as compared to the negative control respectively(P
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Objective:To develop a Wnt-dependent ?-catenin-mediated functional assay system.Methods:To construct a vector,pCMV-bcGFP,which can express the ?-catenin and green fluorescent protein(GFP) fusion protein;transfect HEK293 with the vector,select the cells with G418 and LiCl and establish the stable cell line,293-bc-GFP by cloning.Results:293-bc-GFP stable cell line was developed;the background expression of ?-catenin-GFP fusion protein was detectable at a very low level in the cell line under fluorescent microscope and via Western blotting analysis;however,the fusion protein was showed to significantly increase in the presence of Wnt1 and lithium.Conclusion:Our results showed that the system is regulated by ?-catenin in a Wnt-responsive fasion.Thus,it can be used as a functional reporter to identify potential upstream factors during tumorigenesis,as well as to screen for the potential anti-cancer agents that specifically inhibit ?-catenin signaling in human tumors.