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Cellular and Molecular Neurobiology

, Volume 32, Issue 1, pp 141–147 | Cite as

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

  • Huan Du
  • Pengtao Li
  • Jun Wang
  • Xuemei Qing
  • Weihong Li
Original Research

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.

Keywords

Amyloid-β peptide Receptor for advanced glycation endproducts MMP-2 expression Brain endothelial cells 

Notes

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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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Huan Du
    • 1
  • Pengtao Li
    • 2
  • Jun Wang
    • 3
  • Xuemei Qing
    • 3
  • Weihong Li
    • 2
  1. 1.Department of PathologyTianjin University of Traditional Chinese MedicineTianjinChina
  2. 2.School of Preclinical MedicineBeijing University of Chinese MedicineBeijingChina
  3. 3.China Academy of Chinese Medical SciencesBeijingChina

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