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 language | English (US) |
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Pages (from-to) | 2558-2568 |
Number of pages | 11 |
Journal | American Journal of Transplantation |
Volume | 8 |
Issue number | 12 |
DOIs | |
State | Published - Dec 2008 |
Externally published | Yes |
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)