کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1936061 1050682 2007 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Lef1 regulates COX-2 transcription in chondrocytes
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Lef1 regulates COX-2 transcription in chondrocytes
چکیده انگلیسی

Although the involvement of Wnt/β-catenin signaling pathway in the regulation of COX-2 expression has been suggested, the underlying molecular mechanisms are still unclear. Here, we demonstrate that lymphoid enhancer-binding factor 1 (Lef1) in concert with β-catenin is associated with the transcriptional regulation of the gene encoding COX-2 in mouse chondrocytes. Our results show that co-overexpression of Lef1 and β-catenin synergistically upregulates COX-2 expression. Furthermore, decrease of Lef1 expression using Lef1 siRNA results in the downregulation of COX-2 expression. Using bioinformatic analysis, we identified a conserved Lef1-binding site that is mapped at the 3′ region of the genomic COX-2 locus. In vivo and in vitro binding of Lef1 at the predicted binding site was proved using chromatin immunoprecipitation assays and electrophoretic mobility shift assays, respectively. Moreover, binding of Lef1 and β-catenin to the Lef1-binding site transactivates COX-2 promoter activity. Our results indicate a pivotal role of Lef1 in the regulation of COX-2 transcription in arthritic chondrocytes.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 364, Issue 2, 14 December 2007, Pages 270–275
نویسندگان
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