Increased matrix metalloproteinase 9 activity and mRNA expression in lung ischemia-reperfusion injury.
OBJECTIVE
In lung ischemia-reperfusion injury, neutrophil migration from the vasculature to the interstitial spaces plays a major role in tissue injury. Degradation of the basement membrane, which is composed of extracellular matrix (ECM) molecules, is necessary for neutrophil migration. Matrix metalloproteinases (MMPs) might play a role in ECM degradation in lung ischemia-reperfusion injury. We evaluated the changes in the activity of MMP-2 and MMP-9, and tissue inhibitor of metalloproteinase 1 (TIMP-1) gene expressions using rat lung transplantation models.


METHODS
We divided animals into 4 groups. Groups I and II served as control groups with intact lungs (Group I) and 24-hour cold-preserved lungs (Group II). Groups III and IV received lung grafts after 24-hour cold preservation. The recipient animals were sacrificed 1 hour (Group III) or 24 hours (Group IV) after transplantation. We evaluated lung injury histologically. We assessed MMP activity using zymography. We assessed MMP-2, MMP-9, and TIMP-1 gene expression using biplex reverse transcriptase-polymerase chain reaction method.


RESULTS
In Groups III and IV, we noted severe ischemia-reperfusion injury. We noted no significant difference in enzyme activity and gene expression of MMP-2 between Groups I and IV. The MMP-9 activity and gene expression were low during ischemia and increased on reperfusion. TIMP-1 gene expression was low during ischemia and at the early phase of reperfusion, and showed a dramatic increase at the late phase of reperfusion.


CONCLUSIONS
Matrix metalloproteinase 9, but not MMP-2, may play an important role in ischemia-reperfusion injury. TIMP-1 increases at the late phase of reperfusion and may compensate for the activity of MMP-9.
Yano
M
M
Department of Surgery II, Nagoya City University School of Medicine, Nagoya, Japan.
Omoto
Y
Y
Yamakawa
Y
Y
Nakashima
Y
Y
Kiriyama
M
M
Saito
Y
Y
Fujii
Y
Y
D000818:Animals; D004591:Electrophoresis, Polyacrylamide Gel; D007511:Ischemia / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D016040:Lung Transplantation; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics* / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism*; D023421:Models, Animal; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D015427:Reperfusion Injury / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics*
D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9