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 James Gores

Research output: Contribution to journalArticle

6 Citations (Scopus)

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

Fingerprint

Bile Ducts
Liver Cirrhosis
Wounds and Injuries
Apoptosis Regulatory Proteins
Fibrosis
Liver
Transgenic Mice
Hepatocytes
Apoptosis
Caspase 7
Genetically Modified Animals
In Situ Nick-End Labeling
Bile
Caspase 3
Ligation
Histology
Serum

Keywords

  • Apoptosis
  • Bile infarct
  • Liver fibrosis
  • Stellate cells

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

Cite this

Kahraman, A., Mott, J. L., Bronk, S. F., Werneburg, N. W., Barreyro, F. J., Guicciardi, M. E., ... 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

Overexpression of Mcl-1 attenuates liver injury and fibrosis in the bile duct-ligated mouse. / Kahraman, Alisan; Mott, Justin L.; Bronk, Steven F.; Werneburg, Nathan W.; Barreyro, Fernando J.; Guicciardi, Maria E.; Akazawa, Yuko; Braley, Karen; Craig, Ruth W.; Gores, Gregory James.

In: Digestive Diseases and Sciences, Vol. 54, No. 9, 09.2009, p. 1908-1917.

Research output: Contribution to journalArticle

Kahraman, A, Mott, JL, Bronk, SF, Werneburg, NW, Barreyro, FJ, Guicciardi, ME, Akazawa, Y, Braley, K, Craig, RW & Gores, GJ 2009, 'Overexpression of Mcl-1 attenuates liver injury and fibrosis in the bile duct-ligated mouse', Digestive Diseases and Sciences, vol. 54, no. 9, pp. 1908-1917. https://doi.org/10.1007/s10620-008-0583-5
Kahraman A, Mott JL, Bronk SF, Werneburg NW, Barreyro FJ, Guicciardi ME et al. Overexpression of Mcl-1 attenuates liver injury and fibrosis in the bile duct-ligated mouse. Digestive Diseases and Sciences. 2009 Sep;54(9):1908-1917. https://doi.org/10.1007/s10620-008-0583-5
Kahraman, Alisan ; Mott, Justin L. ; Bronk, Steven F. ; Werneburg, Nathan W. ; Barreyro, Fernando J. ; Guicciardi, Maria E. ; Akazawa, Yuko ; Braley, Karen ; Craig, Ruth W. ; Gores, Gregory James. / Overexpression of Mcl-1 attenuates liver injury and fibrosis in the bile duct-ligated mouse. In: Digestive Diseases and Sciences. 2009 ; Vol. 54, No. 9. pp. 1908-1917.
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