Identifying the regulative role of NF-κB binding sites within promoter region of human matrix metalloproteinase 9 (mmp-9) by TNF-α induction

Hsi Tien Wu*, Syu Sheng Sie, Tang Ching Kuan, Chih-Sheng Lin

*Corresponding author for this work

研究成果: Article同行評審

14 引文 斯高帕斯(Scopus)

摘要

Matrix metalloproteinase 9 (MMP-9), a member of MMP family, is involved in many physiological processes, including cardiovascular disease (CVD). Tumor necrosis factor-α (TNF-α) is considered a cytokine with pleiotropic biological capabilities and leads to the process of CVD when TNF-α is abnormally released and stimulates MMP-9 expression and activation. In this study, we investigated the molecular mechanism of TNF-α-regulated MMP-9 expression. The experimental results confirm that TNF-α could upregulate MMP-9 expression in heart myoblast H9c2 cells of rat. To evaluate the MMP-9 regulation at transcriptional level, a DNA fragment of 2.2 kb (-2168/+18) of human mmp-9 promoter region was cloned and constructed in a vector of luciferase reporter gene. The 2.2-kb sequences were identified as having three candidate nuclear factor-κ B (NF-κB) binding sites: NF-κB I (-1418/-1409), NF-κB II (-626/-617), and NF-κB III (-353/-345). A series of reporter vectors with the mutated NF-κB sites of mmp-9 promoter sequences were constructed and transfected into H9c2 cells. The results show that the NF-κB II binding site (-626/-617) within the promoter region of mmp-9 plays a key role in upregulation of mmp-9 expression by TNF-α induction. In addition, we also first identified that the NF-κB I, similar to c-Rel, might be one of the NF-κB families to regulate mmp-9 expression.

原文English
頁(從 - 到)438-449
頁數12
期刊Applied Biochemistry and Biotechnology
169
發行號2
DOIs
出版狀態Published - 1 一月 2013

指紋 深入研究「Identifying the regulative role of NF-κB binding sites within promoter region of human matrix metalloproteinase 9 (mmp-9) by TNF-α induction」主題。共同形成了獨特的指紋。

引用此