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The Interaction of Amyloid β and the Receptor for Advanced Glycation Endproducts Induces Matrix Metalloproteinase-2 Expression in Brain Endothelial Cells

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Abstract

The pathological hallmarks of Alzheimer’s disease (AD) include formation of extracellular amyloid-β peptide (Aβ) and inflammatory responses. Numerous studies have reported that cerebral microvascular Aβ deposition promotes neuroinflammation in AD. Matrix metalloproteinases (MMPs) are involved in the cleavage of extracellular matrix proteins and regulation of growth factors, receptors, and adhesion molecules. Relatively little is known about the involvement of MMPs as inflammatory mediators in the pathological processes of AD. In this study, we explored the signaling pathway of MMP-2 up-regulation by Aβ in brain endothelial cells (BECs) of mice. Using Western blots, we found that inhibitors of extracellular-signal-regulated kinases (ERK) and c-Jun N-terminal kinase (JNK) significantly decreased Aβ-induced MMP-2 expression in BECs. Furthermore, antibody neutralization of the receptor for advanced glycation endproducts effectively blocked Aβ-induced activation of ERK and JNK and their contribution to elevated MMP-2 expression in BECs. Our results suggest that increased MMP-2 expression induced by the interaction of Aβ with RAGE in BECs may contribute to enhanced vascular inflammatory stress in Aβ-related vascular disorders, such as cerebral amyloid angiopathy and AD. This study offers new insights into neuroinflammation in the progression of AD.

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Acknowledgments

The Grant sponsors are from Ministry of Education and Key laboratory of Chinese Internal Medicine; The National Basic Research Program (Grant No. 2005CB523311); The National significant science and technology special projects (Grant No. 2009ZX0950214).

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Authors and Affiliations

  1. Department of Pathology, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China

    Huan Du

  2. School of Preclinical Medicine, Beijing University of Chinese Medicine, No 11 Bei San Huan East Road, ChaoYang District, Beijing, 100029, China

    Pengtao Li & Weihong Li

  3. China Academy of Chinese Medical Sciences, Beijing, 100700, China

    Jun Wang & Xuemei Qing

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  1. Huan Du
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  2. Pengtao Li
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  3. Jun Wang
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  5. Weihong Li
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Correspondence to Pengtao Li.

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Du, H., Li, P., Wang, J. et al. The Interaction of Amyloid β and the Receptor for Advanced Glycation Endproducts Induces Matrix Metalloproteinase-2 Expression in Brain Endothelial Cells. Cell Mol Neurobiol 32, 141–147 (2012). https://doi.org/10.1007/s10571-011-9744-8

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  • DOI: https://doi.org/10.1007/s10571-011-9744-8

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