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Matrix Metalloproteinase 2 in Reduced‐Size Liver Transplantation: Beyond the Matrix
Author(s) -
PadrissaAltés S.,
Zaouali M. A.,
FrancoGou R.,
Bartrons R.,
Boillot O.,
Rimola A.,
Arroyo V.,
Rodés J.,
Peralta C.,
RosellóCatafau J.
Publication year - 2010
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2010.03092.x
Subject(s) - mmp2 , matrix metalloproteinase , mmp9 , transplantation , downregulation and upregulation , liver transplantation , medicine , matrix metalloproteinase inhibitor , liver regeneration , liver injury , regeneration (biology) , cancer research , microbiology and biotechnology , biology , biochemistry , gene
We studied the contribution of matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) to the beneficial effects of preconditioning (PC) in reduced‐size orthotopic liver transplantation (ROLT). We also examined the role of c‐Jun N‐terminal kinase (JNK) and whether it regulates MMP2 in these conditions. Animals were subjected to ROLT with or without PC and pharmacological modulation, and liver tissue samples were then analyzed. We found that MMP2, but notMMP9, is involved in the beneficial effects of PC in ROLT. MMP2 reduced hepatic injury and enhanced liver regeneration. Moreover, inhibition of MMP2 in PC reduced animal survival after transplantation. JNK inhibition in the PC group decreased hepatic injury and enhanced liver regeneration. Furthermore, JNK upregulated MMP2 in PC. In addition, we showed that Tissue inhibitors of matrix metalloproteinases 2 (TIMP2) was also upregulated in PC and that JNK modulation also altered its levels in ROLT and PC. Our results open up new possibilities for therapeutic treatments to reduce I/R injury and increase liver regeneration after ROLT, which are the main limitations in living‐donor transplantation.