Role of matrix metalloproteinases in cholestasis and hepatic ischemia/reperfusion injury: A review

Giuseppina Palladini, Andrea Ferrigno, Plinio Richelmi, Stefano Perlini, Mariapia Vairetti

Research output: Contribution to journalArticlepeer-review


Matrix metalloproteinases (MMPs) are a family of proteases using zinc-dependent catalysis to break down extracellular matrix (ECM) components, allowing cell movement and tissue reorganization. Like many other proteases, MMPs are produced as zymogens, an inactive form, which are activated after their release from cells. Hepatic ischemia/reperfusion (I/R) is associated with MMP activation and release, with profound effects on tissue integrity: their inappropriate, prolonged or excessive expression has harmful consequences for the liver. Kupffer cells and hepatic stellate cells can secrete MMPs though sinusoidal endothelial cells are a further source of MMPs. After liver transplantation, biliary complications are mainly attributable to cholangiocytes, which, compared with hepatocytes, are particularly susceptible to injury and ultimately a major cause of increased graft dysfunction and patient morbidity. This paper focuses on liver I/R injury and cholestasis and reviews factors and mechanisms involved in MMP activation together with synthetic compounds used in their regulation. In this respect, recent data have demonstrated that the role of MMPs during I/R may go beyond the mere destruction of the ECM and may be much more complex than previously thought. We thus discuss the role of MMPs as an important factor in cholestasis associated with I/R injury.

Original languageEnglish
Pages (from-to)12114-12124
Number of pages11
JournalWorld Journal of Gastroenterology
Issue number42
Publication statusPublished - Nov 14 2015


  • Cholestasis
  • Ischemia/reperfusion
  • Liver
  • Matrix metalloproteinases

ASJC Scopus subject areas

  • Gastroenterology


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