Transient Expression of Reck Under Hepatic Ischemia/Reperfusion Conditions Is Associated with Mapk Signaling Pathways

Andrea Ferrigno, Laura G.Di Pasqua, Giuseppina Palladini, Clarissa Berardo, Roberta Verta, Plinio Richelmi, Stefano Perlini, Debora Collotta, Massimo Collino, Mariapia Vairetti

Research output: Contribution to journalArticlepeer-review

Abstract

In this study, we demonstrated the involvement of matrix metalloproteinases (MMPs) in hepatic ischemia/reperfusion (I/R) injury. Our aim is to evaluate the impact of reperfusion on I/R-related changes in RECK, an MMP modulator, and mitogen-activated protein kinase (MAPKs) pathways (ERK, p38, and JNK). Male Wistar rats were either subjected to 60 min partial-hepatic ischemia or sham-operated. After a 60 min or 120 min reperfusion, liver samples were collected for analysis of MMP-2 and MMP-9 by zymography and RECK, TIMP-1, and TIMP-2 content, MAPKs activation (ERK1/2, JNK1/2, and p38), as well as iNOS and eNOS by Western blot. Serum enzymes AST, ALT, and alkaline-phosphatase were quantified. A transitory decrease in hepatic RECK and TIMPs was associated with a transitory increase in both MMP-2 and MMP-9 activity and a robust activation of ERK1/2, JNK1/2, and p38 were detected at 60 min reperfusion. Hepatic expression of iNOS was maximally upregulated at 120 min reperfusion. An increase in eNOS was detected at 120 min reperfusion. I/R evoked significant hepatic injury in a time-dependent manner. These findings provide new insights into the underlying molecular mechanisms of reperfusion in inducing hepatic injury: a transitory decrease in RECK and TIMPs and increases in both MAPK and MMP activity suggest their role as triggering factors of the organ dysfunction.

Original languageEnglish
JournalBiomolecules
Volume10
Issue number5
DOIs
Publication statusPublished - May 11 2020

Keywords

  • eNOS
  • iNOS.
  • ischemia/reperfusion
  • MAPKs
  • matrix metalloproteinase
  • RECK

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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