Characterization of ischemia/reperfusion-induced gene expression in experimental pancreas transplantation.
BACKGROUND
The aim of this study was to identify genes that are differentially expressed in the early period after pancreatic cold ischemia/reperfusion (I/R) injury.


METHODS
Grafts of isogeneic rat pancreaticoduodenal transplantation were subjected to different preservation solutions and cold ischemia times (CITs): University of Wisconsin (UW), 6-hour CIT; UW, 18-hour CIT; and physiologic saline solution, 6-hour CIT. Animals that did not receive transplants served as controls. At 2-hour reperfusion, grafts were removed and pancreatic RNA was isolated, pooled, and hybridized to Affymetrix RG-U34A arrays. Quantitative reverse-transcription polymerase chain reaction was used to confirm the results of microarray technology.


RESULTS
A total of 49 genes were consistently upregulated (more than threefold) in all three groups of transplant recipient animals. Prominent genes include transcription factors; cytoskeletal factors; heat-shock proteins (e.g. Hsp27, Hsp90); molecules involved in inflammation (e.g. PAPIII), immunology, signal transduction, and translation; and genes that have not been associated with I/R injury so far (e.g. Best5). Messenger RNA levels of some genes were exclusively downregulated in response to the different conditions applied to the pancreatic grafts: Cybb, Reg3a, Per2, BMAL1, MAP, and Isl2.


CONCLUSIONS
These results provide new insight in I/R-induced gene expression after experimental pancreas transplantation. The reported upregulation of heat shock proteins, Best5, and PAPIII may play a pathologic role in pancreatic cold I/R injury and could therefore provide a promising perspective for further investigations.
Drognitz
Oliver
O
University of Freiburg, Department of General and Gastroenterological Surgery, Germany. oliverdrognitz@web.de
Michel
Philip
P
Koczan
Dirk
D
Neeff
Hannes
H
Mikami
Yukio
Y
Obermaier
Robert
R
Thiesen
Hans-Jürgen
HJ
Hopt
Ulrich Theodor
UT
Loebler
Marian
M
D000818:Animals; D050377:Cold Ischemia / Q000009:adverse effects*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D008297:Male; D016035:Pancreas Transplantation; D000073718:Pancreatitis-Associated Proteins; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000378:metabolism*; D019737:Transplants