Overexpression of Mcl-1 attenuates liver injury and fibrosis in the bile duct-ligated mouse

Alisan Kahraman, Justin L. Mott, Steven F. Bronk, Nathan W. Werneburg, Fernando J. Barreyro, Maria E. Guicciardi, Yuko Akazawa, Karen Braley, Ruth W. Craig, Gregory J. Gores

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Hepatocyte apoptosis contributes to liver injury and fibrosis after cholestatic injury. Our aim was to ascertain if the anti-apoptotic protein Mcl-1 alters liver injury or fibrosis in the bile duct-ligated mouse. Markers of apoptosis and fibrosis were compared in wild-type and transgenic mice expressing human Mcl-1 after bile duct ligation. Compared to hMcl-1 transgenic animals, ligated wild-type mice displayed a significant increase in TUNEL-positive cells and in caspase 3/7-positive hepatocytes. Consistent with apoptotic injury, the pro-apoptotic protein Bak underwent a conformational change to an activated form upon cholestatic injury, a change mitigated by hMcl-1 overexpression. Likewise, liver histology, number of bile infarcts, serum ALT values, markers of hepatic fibrosis, and animal survival were improved in bile duct-ligated mice transgenic for hMcl-1 as compared to wild-type mice. In conclusion, increased Mcl-1 expression plays a role in hepatoprotection upon cholestatic liver injury.

Original languageEnglish (US)
Pages (from-to)1908-1917
Number of pages10
JournalDigestive diseases and sciences
Volume54
Issue number9
DOIs
StatePublished - Sep 2009

Keywords

  • Apoptosis
  • Bile infarct
  • Liver fibrosis
  • Stellate cells

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

Fingerprint Dive into the research topics of 'Overexpression of Mcl-1 attenuates liver injury and fibrosis in the bile duct-ligated mouse'. Together they form a unique fingerprint.

  • Cite this

    Kahraman, A., Mott, J. L., Bronk, S. F., Werneburg, N. W., Barreyro, F. J., Guicciardi, M. E., Akazawa, Y., Braley, K., Craig, R. W., & Gores, G. J. (2009). Overexpression of Mcl-1 attenuates liver injury and fibrosis in the bile duct-ligated mouse. Digestive diseases and sciences, 54(9), 1908-1917. https://doi.org/10.1007/s10620-008-0583-5