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Application of the factors activates astrocytes <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>, and their expression as well as their receptors is upregulated after brain injury. Here, we investigated their function by studying M\u00fcller cell activation induced by optic nerve crush in CNTF\u2010 and LIF\u2010deficient mice, and in animals with deficiencies in cytokine signaling pathways. In the retina of CNTF<jats:sup>\u2013\/\u2013<\/jats:sup> mice, basal GFAP expression was reduced, but unexpectedly, injury\u2010induced upregulation in activated M\u00fcller cells was increased during the first 3 days after lesion as compared to wild\u2010type animals and this corresponded with higher phosphorylation level of STAT3, an indicator of cytokine signaling. The observation that LIF expression was strongly upregulated in CNTF<jats:sup>\u2013\/\u2013<\/jats:sup> mice but not in wild\u2010type animals following optic nerve lesion provided a possible explanation. In fact, additional ablation of the LIF gene in CNTF\/LIF double knockout mice almost completely abolished early lesion\u2010induced GFAP upregulation in M\u00fcller cells and STAT3 phosphorylation. Early M\u00fcller cell activation was also eliminated in LIF<jats:sup>\u2013\/\u2013<\/jats:sup> mice, despite normal CNTF levels, as well as in mutants deficient in gp130\/JAK\/STAT signaling and in conditional STAT3 knockout mice. Our results demonstrate that LIF signaling via the gp130\/JAK\/STAT3 pathway is required for the initiation of the astrogliosis\u2010like reaction of retinal M\u00fcller cells after optic nerve injury. A potential role of CNTF was possibly masked by a compensatory increase in LIF signaling in the absence of CNTF. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/glia.20961","type":"journal-article","created":{"date-parts":[[2010,1,20]],"date-time":"2010-01-20T15:48:19Z","timestamp":1264002499000},"page":"768-779","source":"Crossref","is-referenced-by-count":47,"title":["Involvement of gp130\u2010associated cytokine signaling in M\u00fcller cell activation following optic nerve 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