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Egr1: a novel target for ameliorating acute allograft rejection in an experimental lung transplant model.
- Source :
-
European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery [Eur J Cardiothorac Surg] 2012 Mar; Vol. 41 (3), pp. 669-75. - Publication Year :
- 2012
-
Abstract
- 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.<br />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.<br />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).<br />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.
- Subjects :
- Acute Disease
Animals
CD4-CD8 Ratio
Disease Models, Animal
Early Growth Response Protein 1 deficiency
Early Growth Response Protein 1 genetics
Flow Cytometry methods
Gene Expression Regulation
Graft Rejection immunology
Graft Rejection pathology
Graft Rejection prevention & control
Lung Transplantation immunology
Lung Transplantation physiology
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
RNA, Messenger genetics
Real-Time Polymerase Chain Reaction methods
Early Growth Response Protein 1 physiology
Graft Rejection metabolism
Lung Transplantation pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-734X
- Volume :
- 41
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery
- Publication Type :
- Academic Journal
- Accession number :
- 22345187
- Full Text :
- https://doi.org/10.1093/ejcts/ezr030