Egr1: A novel target for ameliorating acute allograft rejection in an experimental lung transplant model

Naohisa Waki, Masaomi Yamane, Sumiharu Yamamoto, Mikio Okazaki, Seiichiro Sugimoto, Akihiro Matsukawa, Takahiro Oto, Shinichiro Miyoshi

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


Objectives: Acute allograft rejection is one of the significant complications occurring in lung transplant recipients. Early growth response-1 (Egr-1), zinc-finger-type transcription factor, is known as a master switch regulator of diverse chemical mediators. We used an orthotopic mouse model of left lung transplant to elucidate the function of Egr-1 in acute pulmonary rejection. Methods: Left lung grafts retrieved from C57BL/6 wild mice or C57BL/6 Egr-1-null mice were orthotopically transplanted into BALB/c mice; the lungs were harvested at day 1, 3, 5 or 7 after lung transplantation. The grade of acute rejection was histopathologically evaluated. The intragraft gene expression levels of Egr-1 and downstream target mediators were quantitatively measured by real-time polymerase chain reaction. Immunohistochemical analysis was used to determine the location and distribution of the Egr-1 protein in the pulmonary graft. Results: Severe acute rejection was observed in allografts from wild-type mice at 5 days after transplantation. Only minimal rejection was seen in the lung graft from Egr-1-null donor mice at 5 days after transplantation. Strong upregulation of Egr-1 mRNA transcripts was observed at day 1, which then decreased during the next 5 days. The mRNA of Egr-1 target mediators [interleukin-1-beta (IL-1β), monocyte chemotactic protein-1 (MCP-1) and plasminogen activator inhibitor-1] reached maximal levels at day 5. Egr-1-null allografts exhibited significantly lower expressions of IL-1β and MCP-1 mRNA (P < 0.05). Conclusions: Our study showed that deletion of Egr-1 in lung allografts ameliorates severe acute rejection with the reduction of expression levels of chemical mediators, implying a new possible strategy for treating acute pulmonary allograft rejection.

Original languageEnglish
Pages (from-to)669-675
Number of pages7
JournalEuropean Journal of Cardio-Thoracic Surgery
Issue number3
Publication statusPublished - Mar 2012


  • Acute rejection
  • Egr-1
  • Inflammatory cytokines
  • Lung transplantation

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine


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