The MAP kinase phosphatase-1 MKP-1/DUSP1 is a regulator of human liver response to transplantation

T. Boutros, A. Nantel, A. Emadali, G. Tzimas, S. Conzen, E. Chevet, P. P. Metrakos

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Orthotopic liver transplantation (OLT) continues to be the only remedy for end-stage liver disease. In an attempt to decrease the ever-widening gap between organ donor and recipient numbers, and ultimately make more livers amenable to transplantation, we characterized the healthy human liver's response to ischemia and reperfusion-induced injury during transplantation. This was carried out by transcriptional profiling using cDNA microarray to identify genes whose expression was modulated at the 1-h postreperfusion time point. We observed that the map kinase phosphatase-1/dual-specificity phosphatase-1 (MKP-1/DUSP1) mRNA was strongly and significantly upregulated. Validation of this observation was carried out using reverse transcriptase-polymerase chain reaction (RT-PCR), immunoblotting and immunohistochemistry. In addition, we characterized the signaling pathways regulating MKP-1 expression using the human hepatoma cell line HepG2. Finally, by combining MKP-1 silencing with reperfusion-associated stresses, we reveal the preferential role of this protein in attenuating the activity of the JNK and p38MAPK pathways, and the resulting apoptosis, making MKP-1 a potential target for therapeutic intervention.

Original languageEnglish (US)
Pages (from-to)2558-2568
Number of pages11
JournalAmerican Journal of Transplantation
Volume8
Issue number12
DOIs
StatePublished - Dec 2008
Externally publishedYes

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Keywords

  • Gene expression profiling
  • Live donor transplantation
  • Liver transplantation
  • Living donor transplantation
  • MAP kinase
  • Signal transduction
  • Signaling
  • Whole liver transplantation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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