DNA array analysis of the developing rat cerebellum: transforming growth factor-beta2 inhibits constitutively activated NF-kappaB in granule neurons.
The nuclear factor-kappaB (NF-kappaB) pathway is important in neuronal survival and in integration of external signals e.g. cytokines, glutamate, Abeta and nerve growth factor (NGF). During rat cerebellar development NF-kappaB activity is high in granule cells before postnatal day 7 (P7) and declines after P7. Using gene expression profiles, measured by cDNA arrays, up-regulation of transforming growth factor-beta2 (TGF-beta2) was correlated with the developmental down-regulation of NF-kappaB. TGF-beta2 depicted strongest, more than 4-fold, up-regulation in P12 versus P4 cerebella. In situ hybridization and immunohistochemistry confined upregulated TGF-beta2 to granule cells and correlated mRNA and TGF-beta2-protein increase. Finally TGF-beta2 repressed NF-kappaB activity, in an in vitro system resembling migrating cerebellar granule cells. Thus, TGF-beta might fulfill an important role in repressing developmentally activated NF-kappaB in granule neurons.
Institut für Neurobiochemie, Universität Witten/Herdecke, D-58448, Witten, Germany.
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Kaltschmidt
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Kaltschmidt
D000818:Animals; D001921:Brain / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D002531:Cerebellum / Q000196:embryology*; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053781:Transforming Growth Factor beta2; D015854:Up-Regulation
D018076:DNA, Complementary; D016328:NF-kappa B; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2