Distinct roles of matrix metalloproteases in the early- and late-phase development of neuropathic pain

Kawasaki, Yuki; Xu, Zhen-Zhong; Wang, Xiaoying; Park, Jong Yeon; Zhuang, Zhijian; Tan, Ping-Heng; Gao, Yong‐Jing; Roy, Kristine; Corfas, Gabriel; Lo, Eng H.; Ji, Ru Rong

doi:10.1038/nm1723

Cited by 682 publications

(817 citation statements)

References 28 publications

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“…striatal neurons and astrocytes increase when compared to control, suggesting that molecular signals released by ''denervated'' neurons and axons support the inflammatory environment. MMP-9 could be a good candidate, as can favor migration of glial cells by cleaving/modifying cell surface receptors, activating chemotactic factors and pro-inflammatory chemokines (IL-1b, TNF-a) (Kawasaki et al 2008), and degrading ECM proteins. On the other hand, TNF-a and IL-1 b induce a prominent release of MMP-9 by glial cells (Kauppinen and Swanson 2005), which in turn amplify their reactive state (Sbai et al 2010), further modifying cell size and enhancing amoeboid movements (Fig.…”

Section: Discussionmentioning

confidence: 99%

Metalloproteinase-9 contributes to inflammatory glia activation and nigro-striatal pathway degeneration in both mouse and monkey models of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism

et al. 2014

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Inflammation is a predominant aspect of neurodegenerative diseases, manifested by glia activation and expression of pro-inflammatory mediators. Studies on animal models of Parkinson's disease (PD) suggest that sustained neuroinflammation exacerbates degeneration of the dopaminergic (DA) nigro-striatal pathway. Therefore, insights into the inflammatory mechanisms of PD may help the development of novel therapeutic strategies against this disease. As extracellular matrix metalloproteinases (MMPs) could be major players in the progression of Parkinsonism, we investigated, in the substantia nigra and striatum of mice acutely injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), changes in mRNA expression, protein levels, and cell localization of MMP-9. This protease is mainly neuronal, but early after MPTP injection its mRNA and protein levels, as well as the number of MMP-9-expressing microglia and astrocytes, increase concomitantly to a prominent inflammation. Neuroinflammation and MMP-9+ glia begin to decline within 2 weeks, although protein levels remain higher than control, in association with a partial recovery of DA nigro-striatal circuit. Comparable quantitative studies on MMP-9 knock-out mice, show a significant decrease in both glia activation and loss of DA neurons and fibers, with respect to wild-type. Moreover, in a parallel study on chronically MPTP-injected macaques, we observed that perpetuation of inflammation and high levels of MMP-9 are associated to DA neuron loss. Our data suggest that MMP-9 released by injured neurons favors glia activation; glial cells in turn reinforce their reactive state via autocrine MMP-9 release, contributing to nigro-striatal pathway degeneration. Specific modulation of MMP-9 activity may, therefore, be a strategy to ameliorate harmful inflammatory outcomes in Parkinsonism. © 2014 Springer-Verlag Berlin Heidelberg

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Section: Discussionmentioning

confidence: 99%

Metalloproteinase-9 contributes to inflammatory glia activation and nigro-striatal pathway degeneration in both mouse and monkey models of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism

et al. 2014

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“…Thus, pioglitazone-primed PPARγ in the neurons and the adipocytes alone may be not enough to prevent tactile allodynia induced by PSL. The pathological role of PPARγ in neurons and adipocytes in neuropathic pain is still unclear, whereas DRGs and spinal neurons can secrete some inflammatory mediators that may be the basis for neuropathic pain (11,12). The adipocytes also can secrete inflammatory cytokines, such as IL-6 and TNF-α (13), which are reportedly essential for neuropathic pain (7).…”

Section: Discussionmentioning

confidence: 99%

Pioglitazone Attenuates Tactile Allodynia and Thermal Hyperalgesia in Mice Subjected to Peripheral Nerve Injury

et al. 2008

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Abstract. To clarify the role of peroxisome proliferator activated receptor γ (PPARγ) in neuropathic pain, we examined the effect of pioglitazone, a PPARγ agonist, on tactile allodynia and thermal hyperalgesia in a neuropathic pain model. Mice were subjected to partial sciatic nerve ligation (PSL) and given pioglitazone (1 -25 mg / kg, p.o.) once daily. PPARγ was distributed in the neurons of the dorsal root ganglion and the dorsal horn of the spinal cord and in the adipocytes at the epineurium of the sciatic nerve in naive mice. PSL elicited tactile allodynia and thermal hyperalgesia for two weeks. Administration of pioglitazone for the first week after PSL attenuated thermal hyperalgesia and tactile allodynia, which was dose-dependent and blocked by GW9662 (2 mg/ kg, i.p.), a PPARγ antagonist. Administration of pioglitazone for the second week also relieved tactile allodynia, but administration one week before PSL had no effect. A single administration of pioglitazone to mice on day 7 of PSL did not alter tactile allodynia and thermal hyperalgesia. PSL-induced upregulation of tumor necrosis factor-α and interleukin-6, which are essential for neuropathic pain, was suppressed by pioglitazone for the first week. This suggests that pioglitazone alleviates neuropathic pain through attenuation of proinflammatory cytokine upregulation by PPARγ stimulation.

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“…In the setting of neuropathic pain, a condition of constant pain in the absence of a stimulus resulting from damage to the nervous system [50], MMP-9 is both necessary and sufficient for producing the neuropathic pain syndrome whereas MMP-2 expression is necessary to maintain neuropathic pain [51]. Even though MMP-9 is active in the early stages with MMP-2 activity increasing at later time points, both MMP-9 and MMP-2 act through cleavage of a cytokine, interleukin-1β.…”

Section: Differential Metalloproteinase Expression Leads To Varying Pmentioning

confidence: 99%

Metalloproteinases in hypertension and cardiac disease: differential expression and mutual regulation

Bosonea

Wang

Odenbach

et al. 2011

Drug Discovery Today: Disease Models

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Arterial hypertension, a condition characterized by sustained elevated blood pressure, is associated with pathological cardiac remodeling (i.e. cardiac hypertrophy and fibrosis) and is a major risk factor for cardiac failure. These processes can be triggered by excess vasoconstrictive agonists, which induce metalloproteinase-dependent shedding of growth factors to transactivate growth factor receptors and initiate disease signaling. Here, we review emerging evidence that agonistactivated metalloproteinases exhibit different expression patterns and mutual transcriptional regulation during the development of hypertension and cardiac remodeling.

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Distinct roles of matrix metalloproteases in the early- and late-phase development of neuropathic pain

Cited by 682 publications

References 28 publications

Metalloproteinase-9 contributes to inflammatory glia activation and nigro-striatal pathway degeneration in both mouse and monkey models of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism

Metalloproteinase-9 contributes to inflammatory glia activation and nigro-striatal pathway degeneration in both mouse and monkey models of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism

Pioglitazone Attenuates Tactile Allodynia and Thermal Hyperalgesia in Mice Subjected to Peripheral Nerve Injury

Metalloproteinases in hypertension and cardiac disease: differential expression and mutual regulation

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