PMID- 22345187
OWN - NLM
STAT- MEDLINE
DCOM- 20120524
LR  - 20120220
IS  - 1873-734X (Electronic)
IS  - 1010-7940 (Linking)
VI  - 41
IP  - 3
DP  - 2012 Mar
TI  - Egr1: a novel target for ameliorating acute allograft rejection in an 
      experimental lung transplant model.
PG  - 669-75
LID - 10.1093/ejcts/ezr030 [doi]
AB  - 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-1beta), 
      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-1beta 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.
FAU - Waki, Naohisa
AU  - Waki N
AD  - Department of Cancer and Thoracic Surgery, Graduate School of Medicine, Dentistry 
      and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
FAU - Yamane, Masaomi
AU  - Yamane M
FAU - Yamamoto, Sumiharu
AU  - Yamamoto S
FAU - Okazaki, Mikio
AU  - Okazaki M
FAU - Sugimoto, Seiichiro
AU  - Sugimoto S
FAU - Matsukawa, Akihiro
AU  - Matsukawa A
FAU - Oto, Takahiro
AU  - Oto T
FAU - Miyoshi, Shinichiro
AU  - Miyoshi S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Eur J Cardiothorac Surg
JT  - European journal of cardio-thoracic surgery : official journal of the European 
      Association for Cardio-thoracic Surgery
JID - 8804069
RN  - 0 (Early Growth Response Protein 1)
RN  - 0 (Egr1 protein, mouse)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Acute Disease
MH  - Animals
MH  - CD4-CD8 Ratio
MH  - Disease Models, Animal
MH  - Early Growth Response Protein 1/deficiency/genetics/*physiology
MH  - Flow Cytometry/methods
MH  - Gene Expression Regulation
MH  - Graft Rejection/immunology/*metabolism/pathology/prevention & control
MH  - Lung Transplantation/immunology/*pathology/physiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - RNA, Messenger/genetics
MH  - Real-Time Polymerase Chain Reaction/methods
EDAT- 2012/02/22 06:00
MHDA- 2012/05/25 06:00
CRDT- 2012/02/21 06:00
PHST- 2012/02/21 06:00 [entrez]
PHST- 2012/02/22 06:00 [pubmed]
PHST- 2012/05/25 06:00 [medline]
AID - ezr030 [pii]
AID - 10.1093/ejcts/ezr030 [doi]
PST - ppublish
SO  - Eur J Cardiothorac Surg. 2012 Mar;41(3):669-75. doi: 10.1093/ejcts/ezr030.