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Göteborgs universitets publikationer

Epidermal growth factor signaling protects from cholestatic liver injury and fibrosis.

Författare och institution:
Jasmin Svinka (-); Sandra Pflügler (-); Markus Mair (-); Hanns-Ulrich Marschall (Institutionen för medicin, avdelningen för molekylär och klinisk medicin); Jan G Hengstler (-); Patricia Stiedl (-); Valeria Poli (-); Emilio Casanova (-); Gerald Timelthaler (-); Maria Sibilia (-); Robert Eferl (-)
Publicerad i:
Journal of molecular medicine (Berlin, Germany),
ISSN:
1432-1440
Publikationstyp:
Artikel, refereegranskad vetenskaplig
Publiceringsår:
2016
Språk:
engelska
Fulltextlänk:
Sammanfattning (abstract):
We have demonstrated that the signal transducer and activator of transcription 3 (STAT3) protects from cholestatic liver injury. Specific ablation of STAT3 in hepatocytes and cholangiocytes (STAT3(∆hc)) aggravated liver damage and fibrosis in the Mdr2(-/-) (multidrug resistance 2) mouse model for cholestatic disease. Upregulation of bile acid biosynthesis genes and downregulation of epidermal growth factor receptor (EGFR) expression were observed in STAT3(∆hc) Mdr2(-/-) mice but the functional consequences of these processes in cholestatic liver injury remained unclear. Here, we show normal canalicular architecture and bile flow but increased amounts of bile acids in the bile of STAT3(∆hc) Mdr2(-/-) mice. Moreover, STAT3-deficient hepatocytes displayed increased sensitivity to bile acid-induced apoptosis in vitro. Since EGFR signaling has been reported to protect hepatocytes from bile acid-induced apoptosis, we generated mice with hepatocyte/cholangiocyte-specific ablation of EGFR (EGFR(∆hc)) and crossed them to Mdr2(-/-) mice. Importantly, deletion of EGFR phenocopied deletion of STAT3 and led to aggravated liver damage, liver fibrosis, and hyperproliferation of K19(+) cholangiocytes. Our data demonstrate hepatoprotective functions of the STAT3-EGFR signaling axis in cholestatic liver disease.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
MEDICIN OCH HÄLSOVETENSKAP ->
Klinisk medicin ->
Gastroenterologi
Postens nummer:
240954
Posten skapad:
2016-08-30 15:15

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