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 Citations (Scopus)

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

Fingerprint

Dual Specificity Phosphatase 1
Phosphotransferases
Transplantation
End Stage Liver Disease
MAP Kinase Signaling System
Liver
Oligonucleotide Array Sequence Analysis
Reperfusion Injury
Reverse Transcriptase Polymerase Chain Reaction
Immunoblotting
Liver Transplantation
Reperfusion
Hepatocellular Carcinoma
Immunohistochemistry
Tissue Donors
Apoptosis
Gene Expression
Cell Line
Messenger RNA
Proteins

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)

Cite this

The MAP kinase phosphatase-1 MKP-1/DUSP1 is a regulator of human liver response to transplantation. / Boutros, T.; Nantel, A.; Emadali, A.; Tzimas, G.; Conzen, S.; Chevet, E.; Metrakos, P. P.

In: American Journal of Transplantation, Vol. 8, No. 12, 12.2008, p. 2558-2568.

Research output: Contribution to journalArticle

Boutros, T. ; Nantel, A. ; Emadali, A. ; Tzimas, G. ; Conzen, S. ; Chevet, E. ; Metrakos, P. P. / The MAP kinase phosphatase-1 MKP-1/DUSP1 is a regulator of human liver response to transplantation. In: American Journal of Transplantation. 2008 ; Vol. 8, No. 12. pp. 2558-2568.
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