<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "EGF/STAT1-maintained ECM1 expression in hepatic homeostasis is\r\ndisrupted by IFNγ/NRF2 in chronic liver diseases"^^ . "In healthy liver, L-TGF-β is stored in the extracellular matrix and stabilized in an inactive form by ECM1. Upon damage, ECM1 production is downregulated, especially in hepatocytes, leading to spontaneous L-TGF-β activation and fibrogenesis. I used in silico promoter analyses, performed in vitro studies in mouse/human hepatocytes and in vivo experiments with different mouse models, to mechanistically delineate maintenance versus downregulation of ECM1 expression under physiological and pathological conditions. I could identify the crosstalk of signaling pathways that maintain or inhibit ECM1 expression. \r\n\r\nIn my thesis, I found that:\r\n(1) In healthy liver, EGF and HGF are mediators of ECM1 expression maintenance. Thereby, EGF signals via EGFR/p-STAT1 S727 to the Ecm1 promoter. The HGF signal as well integrates at STAT1 signaling.\r\n(2) Upon liver damage and injuries:\r\nI. Inflammation-accumulated hepatic IFNγ interferes with EGF signaling through downregulating EGFR. \r\nII. In addition, IFNγ induces STAT1 phosphorylation at Y701, which interferes with binding of p-STAT1 S727 to the Ecm1 gene promoter. \r\nI and II together result in a decreased ECM1 expression.\r\nIII. Further, IFNγ promotes NRF2 nuclear translocation, which binds to the Ecm1 gene promoter and negatively regulates its transcription, leading to inhibition of ECM1 expression. \r\nTaken together, the EGF/EGFR/p-STAT1 S727 pathway that maintains ECM1 expression homeostasis in healthy hepatocytes is disrupted and inhibited by inflammation-accumulated IFNγ and its effects in stressed hepatocytes with the consequence of L-TGF-β activation and hepatic fibrosis. \r\n\r\nIn conclusion, my findings delineate the regulation of ECM1 expression in hepatocytes, which has potential for therapeutic manipulation of its expression with impact on TGF-β availability to treat chronic liver diseases."^^ . "2024" . . . . . . . "Yujia"^^ . "Li"^^ . "Yujia Li"^^ . . . . . . "EGF/STAT1-maintained ECM1 expression in hepatic homeostasis is\r\ndisrupted by IFNγ/NRF2 in chronic liver diseases (PDF)"^^ . . . "060623 PhD Thesis_Yujia Li.pdf"^^ . . . "EGF/STAT1-maintained ECM1 expression in hepatic homeostasis is\r\ndisrupted by IFNγ/NRF2 in chronic liver diseases (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "EGF/STAT1-maintained ECM1 expression in hepatic homeostasis is\r\ndisrupted by IFNγ/NRF2 in chronic liver diseases (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "EGF/STAT1-maintained ECM1 expression in hepatic homeostasis is\r\ndisrupted by IFNγ/NRF2 in chronic liver diseases (Other)"^^ . . . . . . "preview.jpg"^^ . . . "EGF/STAT1-maintained ECM1 expression in hepatic homeostasis is\r\ndisrupted by IFNγ/NRF2 in chronic liver diseases (Other)"^^ . . . . . . "medium.jpg"^^ . . . "EGF/STAT1-maintained ECM1 expression in hepatic homeostasis is\r\ndisrupted by IFNγ/NRF2 in chronic liver diseases (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #34387 \n\nEGF/STAT1-maintained ECM1 expression in hepatic homeostasis is \ndisrupted by IFNγ/NRF2 in chronic liver diseases\n\n" . "text/html" . . . "610 Medizin"@de . "610 Medical sciences Medicine"@en . .