Induction of MIC-1/growth differentiation factor-15 following bile duct injury

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Macrophage inflammatory peptide-1 (MIC-1)/growth/differentiation factor-15 (GDF-15) is a divergent member of the transforming growth factor-β superfamily cloned by others and us. MIC-1/GDF-15 is expressed in the liver, breast, and colon. Studies have demonstrated a growth-inhibiting effect of MIC-1/GDF-15 on colon and breast cancer cell lines in vitro and on tumor growth in vivo. We previously reported that MIC-1 expression is rapidly induced after a wide variety of murine acute and chronic liver injuries including aniline dye administration. I hypothesized, therefore, that MIC-1/GDF-15 may be a mediator of biliary tract injury and could play a role in regulation of bile duct proliferation. C57BL/6 mice underwent surgical ligation of the common bile duct. Northern blot analysis revealed a time-dependent induction of MIC-1/GDF-15 mRNA in the liver. In situ hybridization of liver sections for MIC-1/GDF-15 expression after bile duct ligation demonstrated a zone 1 or periportal expression pattern, consistent with expression of MIC-1 in periductular hepatocytes. Northern blot analysis of liver mRNA from patients with sclerosing cholangitis or cirrhosis also demonstrated enhanced expression of MIC-1/GDF-15. MIC-1/GDF-15 is expressed after bile duct injury in mice and humans. Taken together with the previously demonstrated growth inhibitory effects of MIC-1/GDF-15 on normal and transformed cells, MIC-1/GDF-15 may play a role in regulation of bile duct proliferation and biliary tumor formation.

Original languageEnglish (US)
Pages (from-to)901-905
Number of pages5
JournalJournal of Gastrointestinal Surgery
Issue number7
StatePublished - Nov 2003
Externally publishedYes


  • Cholangiocarcinoma
  • Cytokines
  • Growth substances
  • Inflammation

ASJC Scopus subject areas

  • Surgery
  • Gastroenterology

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