American Journal of Physiology-Gastrointestinal and Liver Physiology · 2021 · 23 citations · 27 references
Life SciencesPathobiologyPathologyCell SignalingSignal TransductionTranscriptional RegulationFibrosisHedgehog SignalingHepatic FibrosisHepatic PathologyHepatic PathophysiologyLiver DiseaseActivated Hepatic Stellate CellsConditional Gene KnockoutHepatic Stellate Cell BiologyHepatic Stellate Cell FunctionImmunofluorescence StainingLiver Stellate Cell ActivationProtein Expression LevelsWestern Blot Analysis
Gli2 is a key transcription effector of Hh signaling. We found that Hh/Gli2 signaling activity was upregulated in CCl 4 -induced liver fibrosis. Conditional deletion of the Gli2 gene in HSCs ameliorated CCl 4 -induced liver fibrosis and HSCs activation. Moreover, Gli2 promoted activation of HSCs through upregulation of cyclin expression and TGF-β signaling activity. Thus, our data provide strong support for future investigations on Gli2 inhibition to slow liver fibrosis progression in humans.
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Erich Roessler, Yangzhu Du, José L. Mullor et al. · Proceedings of the National Academy of Sciences · 2003 · 344 citations · Full text