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Msln/Muc16 signaling in activated Portal Fibroblasts drives the development of cholestatic fibrosis and HCC in aged female Mdr2-/- mice - PubMed

3 hours ago
  • #Portal Fibroblasts
  • #Cholestatic Fibrosis
  • #Hepatocellular Carcinoma
  • Aged female Mdr2-/- mice show increased susceptibility to cholestatic fibrosis and HCC compared to males.
  • Deletion of Msln or Muc16 reduces fibrosis, inflammation, and HCC in Mdr2-/- mice, unlike deletion of Thy-1.
  • Msln- and Muc16-deficient activated portal fibroblasts exhibit a less fibrogenic and inflammatory phenotype.
  • MMP3 from Msln-/- aPFs mediates shedding of hepatic HGFR, suppressing hepatocyte proliferation via HGF-c-Met signaling.
  • Inhibition of MMP3 restores proliferation in human hepatocytes, linking aPF signaling to hepatocyte function regulation.