Induction of MIC-1/growth differentiation factor-15 following bile duct injury.
Macrophage inflammatory peptide-1 (MIC-1)/growth/differentiation factor-15 (GDF-15) is a divergent member of the transforming growth factor-beta 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.
Koniaris
Leonidas G
LG
Department of Surgery, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA. lkoniaris@med.miami.edu
D000007:Abdominal Injuries / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001652:Bile Ducts / Q000254:growth & development / Q000293:injuries*; D016207:Cytokines / Q000096:biosynthesis*; D055436:Growth Differentiation Factor 15; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
D016207:Cytokines; C526140:GDF15 protein, human; C526141:Gdf15 protein, mouse; D055436:Growth Differentiation Factor 15