Matrix Metalloproteinase-14 Both Sheds Cell Surface Neuronal Glial Antigen 2 (NG2) Proteoglycan on Macrophages and Governs the Response to Peripheral Nerve Injury

Nishihara, Tasusku; Remacle, Albert G.; Angert, Mila; Shubayev, Igor; Shiryaev, Sergey A.; Liu, Huaqing; Dolkas, Jennifer; Chernov, Andrei V.; Strongin, Alex Y.; Shubayev, Veronica I.

doi:10.1074/jbc.m114.603431

Cited by 49 publications

(63 citation statements)

References 65 publications

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“…At day 28 post-CCI, TIMP-2 levels normalized, whereas the levels of both proteases remained elevated, relative to naïve nerve, and the TIMP-MMP ratio obviously shifted in favor of MMPs. These patterns of MT1-MMP, MMP-2 and TIMP-2 mRNA expression in CCI nerve are similar to their mRNA and protein expression in crushed nerve [34]. …”

Section: Resultsmentioning

confidence: 81%

“…TIMP-2 both assists MT1–MMP in MMP-2 activation and inhibits an excessive activity of both enzymes [26]. In naïve sciatic nerve, the MT1-MMP, MMP-2 and TIMP-2 transcripts are constitutively expressed [19, 34]. However, the ratio of the TIMP-2 expression level relative to those of the proteases is high, suggesting the repression of the MMP activity [34].…”

Section: Resultsmentioning

confidence: 99%

“…In naïve sciatic nerve, the MT1-MMP, MMP-2 and TIMP-2 transcripts are constitutively expressed [19, 34]. However, the ratio of the TIMP-2 expression level relative to those of the proteases is high, suggesting the repression of the MMP activity [34]. To determine whether there is a shift in the MT1-MMP, MMP-2 or TIMP-2 expression in the rat sciatic nerve over the course of painful mononeuropathy, we performed Taqman qRT-PCR of these genes at days 0 (naive), 1, 3, 5, 7, 14 and 28 after CCI (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Reciprocal relationship between membrane type 1 matrix metalloproteinase and the algesic peptides of myelin basic protein contributes to chronic neuropathic pain

Hong

Remacle

Shiryaev

et al. 2017

Brain, Behavior, and Immunity

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Myelin basic protein (MBP) is an auto-antigen able to induce intractable pain from innocuous mechanical stimulation (mechanical allodynia). The mechanisms provoking this algesic MBP activity remain obscure. Our present study demonstrates that membrane type 1 matrix metalloproteinase (MT1-MMP/MMP-14) releases the algesic MBP peptides from the damaged myelin, which then reciprocally enhance the expression of MT1-MMP in nerve to sustain a state of allodynia. Specifically, MT1-MMP expression and activity in rat sciatic nerve gradually increased starting at day 3 after chronic constriction injury (CCI). Inhibition of the MT1-MMP activity by intraneural injection of the function-blocking human DX2400 monoclonal antibody at day 3 post-CCI reduced mechanical allodynia and neuropathological signs of Wallerian degeneration, including axon demyelination, degeneration, edema and formation of myelin ovoids. Consistent with its role in allodynia, the MT1-MMP proteolysis of MBP generated the MBP69-86-containing epitope sequences in vitro. In agreement, the DX2400 therapy reduced the release of the MBP69-86 epitope in CCI nerve. Finally, intraneural injection of the algesic MBP69-86 and control MBP2-18 peptides differentially induced MT1-MMP and MMP-2 expression in the nerve. With these data we offer a novel, self-sustaining mechanism of persistent allodynia via the positive feedback loop between MT1-MMP and the algesic MBP peptides. Accordingly, short-term inhibition of MT1-MMP activity presents a feasible pharmacological approach to intervene in this molecular circuit and the development of neuropathic pain.

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Section: Resultsmentioning

confidence: 81%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Reciprocal relationship between membrane type 1 matrix metalloproteinase and the algesic peptides of myelin basic protein contributes to chronic neuropathic pain

Hong

Remacle

Shiryaev

et al. 2017

Brain, Behavior, and Immunity

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“…We find that phenylephrine-and GTP␥S-stimulated MMP14 activation release HB-EGF (but not EGF (data not shown)) and that this shedding leads to tyrosine phosphorylation of EGFR. MMP14 is known to release other proteins from the plasma membrane (42). Perhaps GPCRs and heterotrimeric G proteins release other such entities.…”

Section: Discussionmentioning

confidence: 99%

Heterotrimeric G Proteins Directly Regulate MMP14/Membrane Type-1 Matrix Metalloprotease

Overland

Insel

2015

Journal of Biological Chemistry

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Background: Mechanisms underlying GPCR-mediated EGFR transactivation are not fully defined. Results: Heterotrimeric G proteins directly regulate membrane-localized MMP14/MT1-MMP, resulting in HB-EGF release and EGFR transactivation. Conclusion: These results define a previously unrecognized, membrane-delimited mechanism for EGFR transactivation. Significance: This mechanism likely plays a role in settings that involve GPCR-RTK transactivation and may represent new therapeutic opportunities.

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“…30 It is known that PC coverage is varied depending on the tumor phenotype, showing different responsiveness to chemotherapy. 31,32 It has been demonstrated that PCs are present as a defective line in ovarian and colonic adenocarcinoma, while in pancreatic ductal adenocarcinoma and glioblastoma, they form glomeruloid structures. In most tumor types, PCs are present as a continuous line along ECs.…”

mentioning

confidence: 99%

Pericyte-targeting drug delivery and tissue engineering

Kang¹,

Shin²

2016

IJN

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Pericytes are contractile mural cells that wrap around the endothelial cells of capillaries and venules. Depending on the triggers by cellular signals, pericytes have specific functionality in tumor microenvironments, properties of potent stem cells, and plasticity in cellular pathology. These features of pericytes can be activated for the promotion or reduction of angiogenesis. Frontier studies have exploited pericyte-targeting drug delivery, using pericyte-specific peptides, small molecules, and DNA in tumor therapy. Moreover, the communication between pericytes and endothelial cells has been applied to the induction of vessel neoformation in tissue engineering. Pericytes may prove to be a novel target for tumor therapy and tissue engineering. The present paper specifically reviews pericyte-specific drug delivery and tissue engineering, allowing insight into the emerging research targeting pericytes.

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Matrix Metalloproteinase-14 Both Sheds Cell Surface Neuronal Glial Antigen 2 (NG2) Proteoglycan on Macrophages and Governs the Response to Peripheral Nerve Injury

Cited by 49 publications

References 65 publications

Reciprocal relationship between membrane type 1 matrix metalloproteinase and the algesic peptides of myelin basic protein contributes to chronic neuropathic pain

Reciprocal relationship between membrane type 1 matrix metalloproteinase and the algesic peptides of myelin basic protein contributes to chronic neuropathic pain

Heterotrimeric G Proteins Directly Regulate MMP14/Membrane Type-1 Matrix Metalloprotease

Pericyte-targeting drug delivery and tissue engineering

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