title: Role of matrix metalloproteinases in cholestasis and hepatic ischemia/reperfusion injury: A review.
abstract: 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.
authors.affiliation: Giuseppina Palladini, Andrea Ferrigno, Plinio Richelmi, Stefano Perlini, Mariapia Vairetti, Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Palladini
authors.affiliation: Giuseppina Palladini, Andrea Ferrigno, Plinio Richelmi, Stefano Perlini, Mariapia Vairetti, Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ferrigno
authors.affiliation: Giuseppina Palladini, Andrea Ferrigno, Plinio Richelmi, Stefano Perlini, Mariapia Vairetti, Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy.
authors.forename: Plinio
authors.initials: P
authors.lastname: Richelmi
authors.affiliation: Giuseppina Palladini, Andrea Ferrigno, Plinio Richelmi, Stefano Perlini, Mariapia Vairetti, Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Perlini
authors.affiliation: Giuseppina Palladini, Andrea Ferrigno, Plinio Richelmi, Stefano Perlini, Mariapia Vairetti, Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy.
authors.forename: Mariapia
authors.initials: M
authors.lastname: Vairetti
mesh_terms: D000818:Animals; D002779:Cholestasis / Q000150:complications / Q000201:enzymology* / Q000473:pathology; D004789:Enzyme Activation; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008099:Liver / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D015427:Reperfusion Injury / Q000150:complications / Q000201:enzymology* / Q000473:pathology; D015398:Signal Transduction
chemical_list: D018836:Inflammation Mediators; D020782:Matrix Metalloproteinases
keywords: Cholestasis; Ischemia/reperfusion; Liver; Matrix metalloproteinases