Egr-1 Mediates SiO2-driven Transcription of Membrane Type Ⅰ Matrix Metalloproteinase in Macrophages
- Author:
Fei XIANG
1
;
Ming BAI
;
Yang JIN
;
Wanli MA
;
Jianbao XIN
Author Information
1. 华中科技大学同济医学院附属协和医院
- Keywords:
silicosis;
Egr-1;
MT1-MMP;
decoy stratey;
macrophage
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2007;27(1):13-16
- CountryChina
- Language:Chinese
-
Abstract:
The up-regulation mechanism of membrane type Ⅰ matrix metalloproteinase (MT1-MMP) in macrophages stimulated by silica in vitro and the contribution of early growth response 1 (Egr-1) transcription factor in the gene expression pathway were investigated. Macrophages stimulated by silica were treated with Egr-1 antibody or Egr-1 decoy oligodeoxynucleotides (ODN). The levels of MT1-MMP proteins were determined by Western blot and the expression of MT1-MMP mRNAs was detected by RT-PCR. The results showed as compared with control macrophages, silica-stimulated group showed up-regulated gene expression of MT1-MMP via Egr-1 (P＜0.01). Compared with silica-stimulated macrophages untreated with antibody, the cells treated with 5 μg/mL Egr-1 antibody were associated with reduced expression of MTI-MMP protein (P＜0.01) and mRNA (P＜0.01). Compared with silica-stimulated untransfected group, the Egr-1 "decoy" ODN group was associated with reduction in the expression of MT1-MMP protein and mRNA (P＜0.01). It was concluded gene expression of MT1-MMP which may play a critical role in silicosis was up-regulated by silica in macrophages. Egr-1 participated in the expression of MT1-MMP and positively regulated the expression. Both Egr-1 antibody and Egr-1 decoy ODN suppressed the expression of MT1-MMP through the Egr-1 pathway and may become a potential therapeutic tool in the management of silicosis in the future.
