Increased matrix metalloproteinase 9 activity and mRNA expression in lung ischemia-reperfusion injury

J Heart Lung Transplant. 2001 Jun;20(6):679-86. doi: 10.1016/s1053-2498(01)00250-9.


Objectives: 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.

MeSH terms

  • Animals
  • Electrophoresis, Polyacrylamide Gel
  • Ischemia / genetics*
  • Ischemia / metabolism*
  • Ischemia / pathology
  • Lung / blood supply*
  • Lung / metabolism*
  • Lung / pathology
  • Lung Transplantation*
  • Male
  • Matrix Metalloproteinase 2 / genetics*
  • Matrix Metalloproteinase 2 / metabolism*
  • Matrix Metalloproteinase 9 / genetics*
  • Matrix Metalloproteinase 9 / metabolism*
  • Models, Animal
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism*
  • Rats
  • Rats, Inbred F344
  • Reperfusion Injury / genetics*
  • Reperfusion Injury / metabolism*
  • Reperfusion Injury / pathology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tissue Inhibitor of Metalloproteinase-1 / genetics*


  • RNA, Messenger
  • Tissue Inhibitor of Metalloproteinase-1
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9