title: Lung matrix metalloproteinase activation following partial hepatic ischemia/reperfusion injury in rats.
abstract: OBJECTIVE
  Warm hepatic ischemia-reperfusion (I/R) injury can lead to multiorgan dysfunction. The aim of the present study was to investigate whether acute liver I/R does affect the function and/or structure of remote organs such as lung, kidney, and heart via modulation of extracellular matrix remodelling.
  
  
  METHODS
  Male Sprague-Dawley rats were subjected to 30 min partial hepatic ischemia by clamping the hepatic artery and the portal vein. After a 60 min reperfusion, liver, lung, kidney, and heart biopsies and blood samples were collected. Serum hepatic enzymes, creatinine, urea, Troponin I and TNF-alpha, and tissue matrix metalloproteinases (MMP-2, MMP-9), myeloperoxidase (MPO), malondialdehyde (MDA), and morphology were monitored.
  
  
  RESULTS
  Serum levels of hepatic enzymes and TNF-alpha were concomitantly increased during hepatic I/R. An increase in hepatic MMP-2 and MMP-9 activities was substantiated by tissue morphology alterations. Notably, acute hepatic I/R affect the lung inasmuch as MMP-9 activity and MPO levels were increased. No difference in MMPs and MPO was observed in kidney and heart.
  
  
  CONCLUSIONS
  Although the underlying mechanism needs further investigation, this is the first study in which the MMP activation in a distant organ is reported; this event is probably TNF-alpha-mediated and the lung appears as the first remote organ to be involved in hepatic I/R injury.
authors.affiliation: Department of Internal Medicine and Therapeutics, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Via Ferrata 9A, 27100 Pavia, Italy.
authors.forename: Giuseppina
authors.identifier: 0000-0003-1312-7513
authors.initials: G
authors.lastname: Palladini
authors.affiliation: Department of Internal Medicine and Therapeutics, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Via Ferrata 9A, 27100 Pavia, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ferrigno
authors.affiliation: Department of Molecular Medicine, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, 27100 Pavia, Italy.
authors.forename: Vittoria
authors.initials: V
authors.lastname: Rizzo
authors.affiliation: Department of Biology and Biotechnology "Lazzaro Spallanzani," University of Pavia, 27100 Pavia, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Tarantola
authors.affiliation: Department of Biology and Biotechnology "Lazzaro Spallanzani," University of Pavia, 27100 Pavia, Italy.
authors.forename: Vittorio
authors.identifier: 0000-0002-5987-4373
authors.initials: V
authors.lastname: Bertone
authors.affiliation: Department of Biology and Biotechnology "Lazzaro Spallanzani," University of Pavia, 27100 Pavia, Italy ; Institute of Molecular Genetics of the C.N.R. (IGM-CNR), Histochemistry and Cytometry Section, University of Pavia, 27100 Pavia, Italy.
authors.forename: Isabel
authors.identifier: 0000-0003-4452-137X
authors.initials: I
authors.lastname: Freitas
authors.affiliation: Department of Internal Medicine and Therapeutics, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Via Ferrata 9A, 27100 Pavia, Italy.
authors.forename: Stefano
authors.identifier: 0000-0002-0320-8574
authors.initials: S
authors.lastname: Perlini
authors.affiliation: Department of Internal Medicine and Therapeutics, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Via Ferrata 9A, 27100 Pavia, Italy.
authors.forename: Plinio
authors.identifier: 0000-0003-1068-6854
authors.initials: P
authors.lastname: Richelmi
authors.affiliation: Department of Internal Medicine and Therapeutics, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Via Ferrata 9A, 27100 Pavia, Italy.
authors.forename: Mariapia
authors.identifier: 0000-0002-2464-6127
authors.initials: M
authors.lastname: Vairetti
mesh_terms: D000818:Animals; D003404:Creatinine / Q000097:blood; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D009928:Organ Specificity; D009195:Peroxidase / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology* / Q000378:metabolism; D019210:Troponin I / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014508:Urea / Q000097:blood
chemical_list: D019210:Troponin I; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D014508:Urea; D003404:Creatinine; D009195:Peroxidase; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat