title: The interaction of amyloid β and the receptor for advanced glycation endproducts induces matrix metalloproteinase-2 expression in brain endothelial cells.
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.
authors.affiliation: Department of Pathology, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Du
authors.forename: Pengtao
authors.initials: P
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Xuemei
authors.initials: X
authors.lastname: Qing
authors.forename: Weihong
authors.initials: W
authors.lastname: Li
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D001921:Brain / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D002561:Cerebrovascular Disorders / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D042783:Endothelial Cells / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011485:Protein Binding / Q000502:physiology; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism* / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse