engleski

Suppression of Smad-1 mRNA expression level by Smad-2 likely control dichotomy of NF-κB and Smads mediated activation

The aim of this study was to find out how NF-κB and Smad-mediated signaling influenced the expression of astrogliogenic versus neurogenic markers of brain development in U4C cells which were either enriched (Tg Jak-1) or deprived in Jak-1 molecule (Jak-1 KO). Genetically modified U4C cells were transfected with NF-kB reporter plasmid in order to follow its activation when cells were cotransfected with different combinations of Smads constructs. In wild type cells no significant activation of NF-κB was observed while genetically modified cells exhibited somewhat different pattern of NF-κB activation depending on the Smad constructs combination used. The absence of NF-κB activation in Jak-1 transgenic cells transfected with Smad-1 plus Smad-3 was accompanied by the appearance of apoptotic cells as revealed by DAPI staining. Smad-1 expression was undetectable in Jak-1 transgenic cells and was downregulated in wild type cells upon transfection with Smad-2. The absence of p65 nuclear translocation in Smad-2 transfected cells and the presence of Smad-4 in nucleus of the same cells indicates dichotomy in NF-κB and Smads mediated signaling pathways. The significance of this study is that helps to elucidate the point of collaboration among three different signaling pathways - Jak-1 mediated cytokine signaling, NF-κB and Smads mediated pathways.

Jak-1 signaling; NF-κB transcription factor; Smads mediators

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