Format

Send to:

Choose Destination
See comment in PubMed Commons below
Appl Biochem Biotechnol. 2013 Jan;169(2):438-49. doi: 10.1007/s12010-012-9958-3. Epub 2012 Dec 6.

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

Author information

  • 1Department of BioAgricultural Science, National Chia Yi University, 300 Syuefu Rd., Chiayi 60004, Taiwan. htwu@mail.ncyu.edu.tw

Abstract

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.

PMID:
23224948
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Springer
    Loading ...
    Write to the Help Desk