Induction of matrix metalloproteinases (MMP3, MMP12 and MMP13) expression in the microglia by amyloid-β stimulation via the PI3K/Akt pathway

Ito, Sachiko; Kimura, Kenta; Haneda, Masataka; Ishida, Yoshiyuki; Sawada, Makoto; Isobe, Ken‐ichi

doi:10.1016/j.exger.2006.11.012

Cited by 81 publications

(53 citation statements)

References 25 publications

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“…A␤-triggered PI3K activation has been implicated in the expression of chemokines in microglia (60,61). However, there is no report about the PI3K signaling pathway coupled to chemokine receptor CCR5 expression.…”

Section: Discussionmentioning

confidence: 97%

Amyloid β Interaction with Receptor for Advanced Glycation End Products Up-Regulates Brain Endothelial CCR5 Expression and Promotes T Cells Crossing the Blood-Brain Barrier

Shang²,

Zhao³

et al. 2009

The Journal of Immunology

104

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How circulating T cells infiltrate into the brain in Alzheimer disease (AD) remains unclear. We previously reported that amyloid β (Aβ)-dependent CCR5 expression in brain endothelial cells is involved in T cell transendothelial migration. In this study, we explored the signaling pathway of CCR5 up-regulation by Aβ. We showed that inhibitors of JNK, ERK, and PI3K significantly decreased Aβ-induced CCR5 expression in human brain microvascular endothelial cells (HBMECs). Chromatin immunoprecipitation assay revealed that Aβ-activated JNK, ERK, and PI3K promoted brain endothelial CCR5 expression via transcription factor Egr-1. Furthermore, neutralization Ab of receptor for advanced glycation end products (RAGE; an Aβ receptor) effectively blocked Aβ-induced JNK, ERK, and PI3K activation, contributing to CCR5 expression in HBMECs. Aβ fails to induce CCR5 expression when truncated RAGE was overexpressed in HBMECs. Transendothelial migration assay showed that the migration of MIP-1α (a CCR5 ligand)-expressing AD patients’ T cells through in vitro blood-brain barrier model was effectively blocked by anti-RAGE Ab, overexpression of truncated RAGE, and dominant-negative PI3K, JNK/ERK, or Egr-1 RNA interference in HBMECs, respectively. Importantly, blockage of intracerebral RAGE abolished the up-regulation of CCR5 on brain endothelial cells and the increased T cell infiltration in the brain induced by Aβ injection in rat hippocampus. Our results suggest that intracerebral Aβ interaction with RAGE at BBB up-regulates endothelial CCR5 expression and causes circulating T cell infiltration in the brain in AD. This study may provide a new insight into the understanding of inflammation in the progress of AD.

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Section: Discussionmentioning

confidence: 97%

Amyloid β Interaction with Receptor for Advanced Glycation End Products Up-Regulates Brain Endothelial CCR5 Expression and Promotes T Cells Crossing the Blood-Brain Barrier

Shang²,

Zhao³

et al. 2009

The Journal of Immunology

104

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“…Matrix metalloproteinases (MMPs) are a family of secreted or transmembrane zinc-dependent endopeptidases. The activation of MMP3, MMP12 and MMP13 was correlated with activation of the PI3K/Akt signaling cascade in microglial cells [32] . In epithelial cells and fibroblasts, MMP12 and MMP13 could be up-regulated in a PI3K, PKCδ and ERK1/2-dependent manner [33] .…”

Section: Discussionmentioning

confidence: 99%

Multiple signaling pathways involved in stimulation of osteoblast differentiation by N-methyl-D-aspartate receptors activation in vitro

Zhao

Cui

et al. 2011

Acta Pharmacol Sin

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Aim: Glutamate receptors are expressed in osteoblastic cells. The present study was undertaken to investigate the mechanisms underlying the stimulation of osteoblast differentiation by N-methyl-D-aspartate (NMDA) receptor activation in vitro. Methods: Primary culture of osteoblasts was prepared from SD rats. Microarray was used to detect the changes of gene expression. The effect of NMDA receptor agonist or antagonist on individual gene was examined using RT-PCR. The activity of alkaloid phosphotase (ALP) was assessed using a commercial ALP staining kit. Results: Microarray analyses revealed that 10 genes were up-regulated by NMDA (0.5 mmol/L) and down-regulated by MK801 (100 μmol/L), while 13 genes down-regulated by NMDA (0.5 mmol/L) and up-regulated by MK801 (100 μmol/L). Pretreatment of osteoblasts with the specific PKC inhibitor Calphostin C (0.05 μmol/L), the PKA inhibitor H-89 (20 nmol/L), or the PI3K inhibitor wortmannin (100 nmol/L) blocked the ALP activity increase caused by NMDA (0.5 mmol/L). Furthermore, NMDA (0.5 mmol/L) rapidly increased PI3K phosphorylation, which could be blocked by pretreatment of wortmannin (100 nmol/L). Conclusion:The results suggest that activation of NMDA receptors stimulates osteoblasts differentiation through PKA, PKC, and PI3K signaling pathways, which is a new role for glutamate in regulating bone remodeling.

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“…Even if their specific pathways have not yet been completely elucidated, many other factors have been described to induce MMP-12 expression: low molecular fragments of hyaluronan, an extracellular matrix glycosaminoglycan that accumulate at sites of lung inflammation [62], amyloid-β peptide in the microglia through PI3K/Akt pathway [63], VEGF (vascular endothelial growth factor) [53], TNF-α (tumor necrosis factor-α) [37], the substance P, most likely through IL-1β and TNF-α [64], CD40 receptor ligand binding on macrophage cell surface [3] and cigarette smoke [65] as a result of massive production of reactive oxygen species during cigarette combustion. Hydrogen peroxidedependent pathway involving NADPH oxidase, AP-1 and TNF-α has been pointed out by Lavigne et al [17] as regulating MMP-12 gene expression.…”

Section: A C C E P T E D Article In Pressmentioning

confidence: 99%

Matrix metalloproteinase 12 silencing: A therapeutic approach to treat pathological lung tissue remodeling?

Garbacki¹,

Valentin²,

Piette³

et al. 2009

Pulmonary Pharmacology & Therapeutics

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Induction of matrix metalloproteinases (MMP3, MMP12 and MMP13) expression in the microglia by amyloid-β stimulation via the PI3K/Akt pathway

Cited by 81 publications

References 25 publications

Amyloid β Interaction with Receptor for Advanced Glycation End Products Up-Regulates Brain Endothelial CCR5 Expression and Promotes T Cells Crossing the Blood-Brain Barrier

Amyloid β Interaction with Receptor for Advanced Glycation End Products Up-Regulates Brain Endothelial CCR5 Expression and Promotes T Cells Crossing the Blood-Brain Barrier

Multiple signaling pathways involved in stimulation of osteoblast differentiation by N-methyl-D-aspartate receptors activation in vitro

Matrix metalloproteinase 12 silencing: A therapeutic approach to treat pathological lung tissue remodeling?

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