RGD Reference Report - Benzopyrene induces expression of matrix metalloproteinases and cell migration and invasion of vascular smooth muscle cells. - Rat Genome Database

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Benzopyrene induces expression of matrix metalloproteinases and cell migration and invasion of vascular smooth muscle cells.

Authors: Meng, D  Lv, DD  Zhuang, X  Sun, H  Fan, L  Shi, XL  Fang, J 
Citation: Meng D, etal., Toxicol Lett. 2009 Jan 10;184(1):44-9. doi: 10.1016/j.toxlet.2008.10.016. Epub 2008 Oct 28.
RGD ID: 7207394
Pubmed: PMID:19022365   (View Abstract at PubMed)
DOI: DOI:10.1016/j.toxlet.2008.10.016   (Journal Full-text)

Benzo[a]pyrene (B[a]P) has been shown to accelerate atherosclerosis development in animal models. However, the mechanisms that B[a]P induces atherogenesis are unclear. Abnormal migration and invasion of vascular smooth muscle cells (VSMCs) is a major contributor to the development of atherosclerotic lesions. In this article, we demonstrated that B[a]P promoted the migration and invasion of rat VSMCs. B[a]P increased the mRNA levels of matrix metalloproteinase (MMP) 1, 2, 3, and 9. The MMPs inhibitor GM6001 inhibited B[a]P-induced invasion of VSMCs. Among the MMPs mentioned above, MMP-3 had the maximal induction. Mechanistic studies indicate that B[a]P-induced transcriptional activation of MMP-3 is not mediated by AP-1, NF-kappaB. B[a]P-induced expression of MMPs was attenuated by alpha-naphthoflavone, the aryl hydrocarbon receptor antagonist. In addition, alpha-naphthoflavone inhibited B[a]P-induced migration and invasion of VSMCs. These results suggest that the aryl hydrocarbon receptor plays an important role in B[a]P-induced expression of MMPs and migration and invasion of VSMC. Our findings may reveal a novel role of B[a]P in inducing atherogenesis.

Objects referenced in this article
Gene Mmp1 matrix metallopeptidase 1 Rattus norvegicus

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