Mitogen-activated protein kinases regulate HO-1 gene transcription after ischemia-reperfusion lung injury Academic Article uri icon


MeSH Major

  • Gene Expression Regulation, Enzymologic
  • Heme Oxygenase (Decyclizing)
  • Lung Diseases
  • MAP Kinase Signaling System
  • Reperfusion Injury


  • Lung ischemia-reperfusion (I-R) is an important model of oxidant-mediated acute lung and vascular injury. Heme oxygenase-1 (HO-1) is a cytoprotective gene that is markedly induced by lung I-R injury. HO-1 mRNA is increased in mouse lung after 30 min of lung hilar clamping (ischemia) followed by 2-6 h of unclamping (reperfusion) compared with control mice. In a variety of vascular cell types, HO-1 mRNA is induced after 24 h of anoxia followed by 30 min-1 h of reoxygenation (A-R). Transfection studies reveal that the promoter and 5'-distal enhancer E1 are necessary and sufficient for increased HO-1 gene transcription after A-R. Immunoblotting studies show all three subfamilies of MAPKs (ERK, JNK, and p38) are activated by 15 min of reperfusion. We also demonstrate that HO-1 gene transcription after A-R involves ERK, JNK, and p38 MAPK pathways. Together, our data show that I-R not only induces HO-1 gene expression in mouse lungs and vascular cells but that gene transcription occurs via the promoter and E1 enhancer and involves upstream MAPK pathways.

publication date

  • October 2002



  • Academic Article



  • eng

PubMed ID

  • 12225959

Additional Document Info

start page

  • L815

end page

  • 29


  • 283


  • 4 27-4