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Identifying the Regulative Role of NF-κB Binding Sites Within Promoter Region of Human Matrix Metalloproteinase 9 (mmp-9) by TNF-α Induction

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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.

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Acknowledgment

This work was supported by the grants of NSC 97-2313-B-415-005-MY3 from the National Science Council, Taiwan.

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  1. Department of BioAgricultural Science, National Chia Yi University, 300 Syuefu Rd., Chiayi, 60004, Taiwan

    Hsi Tien Wu & Syu Sheng Sie

  2. Department of Biological Science and Technology, National Chiao Tung University, Hsin Chu, Taiwan

    Tang Ching Kuan & Chih Sheng Lin

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  1. Hsi Tien Wu
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Wu, H.T., Sie, S.S., Kuan, T.C. et al. Identifying the Regulative Role of NF-κB Binding Sites Within Promoter Region of Human Matrix Metalloproteinase 9 (mmp-9) by TNF-α Induction. Appl Biochem Biotechnol 169, 438–449 (2013). https://doi.org/10.1007/s12010-012-9958-3

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