engleski

JAK-1/Smad signaling dependent genes expression associated with the neurogenic to astrogliogenic transition point of brain development

As the crucial astrogliogenic pathway which could be modulated by variety of environmetal factors, JAK/STAT cytokine signaling represents basically the path that has to be converted in order to transform reactive gliosis into purposeful repair raection in a therapeutical approach of brain damage.Though loss of function studies have helpe to clearify the role of some of its components like LIF or gp130, which turned out to be essential for asrtrolial differentiation, the role of JAK-1 molecule in this process remains elusive. It seems that depending on the preactivation level of JAK/STAT signaling at a given time point during development, depends the final outcome of the interactions among molecules basically defined as astrogliogenic like these are the members of TGF-beta superfamily. Therefore, to address the question on brain development, we have used two cell lines of nonneural origin: one that is deficient in JAK-1 molecule and the other overexpressing it. Upon their transfection with TGF-beta receptor associated molecules, Flagged SMAD-3, -2 or -1, the expression pattern of astrogliogenic versus neurogenic molecules has been followed. The activation status of NF-kB pathway which seems to be equally needed for both neuronal and astroglial differentiation was examined as well. We hope that by dissecting signaling events behind the process of reactive gliosis induced by all types of central nervous system injuries, will get better clue on how to approach the problem of a repair process in adult brain.

brain injury; astrocytes hypertrophy; cytokine signaling; NF-kB signaling

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