Duenker, N.N.DuenkerValenciano, A. I.A. I.ValencianoFranke, A.A.FrankeHernandez-Sanchez, C.C.Hernandez-SanchezDressel, RalfRalfDresselBehrendt, MaikMaikBehrendtDe Pablo, F.F.De PabloKrieglstein, KerstinKerstinKrieglsteinde la Rosa, E. J.E. J.de la Rosa2018-11-072018-11-072005https://resolver.sub.uni-goettingen.de/purl?gro-2/25490Transforming growth factor (TGF)-beta and insulin display opposite effects in regulating programmed cell death during vertebrate retina development; the former induces apoptosis while the latter prevents it. In the present study we investigated coordinated actions of TGF-beta and insulin in an organotypic culture system of early postnatal mouse retina. Addition of exogenous TGF-beta resulted in a significant increase in cell death whereas exogenous insulin attenuated apoptosis and was capable of blocking TGF-beta-induced apoptosis. This effect appeared to be modulated via insulin-induced transcriptional down-regulation of TGF-beta receptor II levels. The analysis of downstream signalling molecules also revealed opposite effects of both factors; insulin provided survival signalling by increasing the level of anti-apoptotic Bcl-2 protein expression and phosphorylation and down-regulating caspase 3 activity whereas pro-apoptotic TGF-beta signalling reduced Bcl-2 mRNA levels and Bcl-2 phosphorylation and induced the expression of TGF-induced immediate-early gene (TIEG), a Kruppel-like zinc-finger transcription factor, mimicking TGF-beta activity.journal_article10.1111/j.1460-9568.2005.04183.x16029193000230577400004