Plasminogen activator inhibitor type 1 regulates microglial motility and phagocytic activity

Jeon, Hyejin; Kim, Jong‐Heon; Kim, Jae Hong; Lee, Won‐Ha; Lee, Myung-Shik; Suk, Kyoungho

doi:10.1186/1742-2094-9-149

Cited by 87 publications

(85 citation statements)

References 107 publications

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“…Primary Culture of Microglia and Cortical Neurons-Primary microglia cultures were prepared as described previously (32). Primary cultures of dissociated cerebral cortical neurons were prepared from embryonic day 20 ICR mice, as described previously (33,34).…”

Section: Methodsmentioning

confidence: 99%

Role of Lipocalin-2-Chemokine Axis in the Development of Neuropathic Pain following Peripheral Nerve Injury

Jeon

Jha

Ock

et al. 2013

Journal of Biological Chemistry

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Background:In the central nervous system, the role of LCN2 as a chemokine inducer has been previously reported. Results: Peripheral nerve injury increased LCN2 expression. Lcn2 deficiency attenuated pain hypersensitivity, microglial activation, and chemokine production. Chemokine expression and pain behavior were induced by LCN2. Conclusion: The LCN2-chemokine axis plays a critical role in the pathogenesis of neuropathic pain. Significance: LCN2 can be targeted for treatment of neuropathic pain.

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Section: Methodsmentioning

confidence: 99%

Role of Lipocalin-2-Chemokine Axis in the Development of Neuropathic Pain following Peripheral Nerve Injury

Jeon

Jha

Ock

et al. 2013

Journal of Biological Chemistry

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“…PAI-1 produced within the brain by microglia and astrocytes may regulate apoptosis, survival of neurites and migration of microglia(Ahn et al, 1999; Jeon et al, 2012; Soeda et al, 2008; Soeda et al, 2001). In vitro experiments examining the role of PAI-1 show that sufficient PAI-1 in the extracellular environments of neurons prevents apoptotic changes (Soeda et al, 2008; Soeda et al, 2001).…”

Section: Plasminogen Activator Inhibitor-1mentioning

confidence: 99%

“…PAI-1 prevents the disintegration of formed neuronal networks by maintaining or promoting neuroprotective signalling through the MAPK/ERK pathway (Soeda et al, 2008). Furthermore, PAI-1 promotes the migration of microglial cells in culture via the low-density lipoprotein receptor-related protein (LRP) 1/Janus kinase (JAK)/signal transducer and activator of transcription (STAT)1 axis (Jeon et al, 2012). Several other cell culture studies indicate that glia-derived PAI-1 may regulate microglial migration in an autocrine or paracrine manner (Ahn et al, 1999; Jeon et al, 2012).…”

Section: Plasminogen Activator Inhibitor-1mentioning

confidence: 99%

“…Furthermore, PAI-1 promotes the migration of microglial cells in culture via the low-density lipoprotein receptor-related protein (LRP) 1/Janus kinase (JAK)/signal transducer and activator of transcription (STAT)1 axis (Jeon et al, 2012). Several other cell culture studies indicate that glia-derived PAI-1 may regulate microglial migration in an autocrine or paracrine manner (Ahn et al, 1999; Jeon et al, 2012). Microglia, the resident macrophages of the CNS, constitute the brain's innate immune system and play a pivotal role in neuroinflammation and host defense against microbial agents (Block et al, 2007; Garden and Moller, 2006; Graeber and Streit, 2010; Jeon et al, 2012; Mallat et al, 2005; Woo et al, 2008).…”

Section: Plasminogen Activator Inhibitor-1mentioning

confidence: 99%

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Obesity and dementia: Adipokines interact with the brain

Arnoldussen

Kiliaan

Gustafson

2014

European Neuropsychopharmacology

187

161

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Obesity is a pandemic and a serious global health concern. Obesity is a risk factor for multiple conditions and contributes to multi-morbidities, resulting in increased health costs and millions of deaths each year. Obesity has been associated with changes in brain structure, cognitive deficits, and dementia and Alzheimer's disease. Adipokines, defined as hormones, cytokines and peptides secreted by adipose tissue, may have more widespread influence and functionality in the brain than previously thought. In this review, six adipokines, and their actions in the obese and non-obese condition will be discussed. Included are: plasminogen activator inhibitor-1 (PAI-1), interleukin-6 (IL-6), tumor necrosis factors alpha (TNF-α), angiotensinogen (AGT), adiponectin and leptin. Their functionality in the periphery, their ability to cross the blood brain barrier (BBB) and their influence on dementia processes within the brain will be discussed.

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“…Pgrmc1 could also interact with other proteins intracellularly. In addition to its binding of P450 components noted above, another partner is plasminogen activator inhibitor 1 (PAI1) RNA binding protein (PAIRBP1), also called SERPINE1 mRNA-binding protein (SERBP1) (40), which can influence microglial motility via levels of PAI1 (41).…”

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confidence: 99%

Progesterone Antagonism of Neurite Outgrowth Depends on Microglial Activation via Pgrmc1/S2R

et al. 2013

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Neuronal plasticity is regulated by the ovarian steroids estradiol (E2) and progesterone (P4) in many normal brain functions, as well as in acute response to injury and chronic neurodegenerative disease. In a female rat model of axotomy, the E2-dependent compensatory neuronal sprouting is antagonized by P4. To resolve complex glial-neuronal cell interactions, we used the "woundingin-a-dish" model of neurons cocultured with astrocytes or mixed glia (microglia to astrocytes, 1:3). Although both astrocytes and mixed glia supported E2-enhanced neurite outgrowth, P4 antagonized E2-induced neurite outgrowth only with mixed glia, but not astrocytes alone. We now show that P4-E2 antagonism of neurite outgrowth is mediated by microglial expression of progesterone receptor (Pgr) membrane component 1 (Pgrmc1)/S2R, a putative nonclassical Pgr mediator with multiple functions. The P4-E2 antagonism of neurite outgrowth was restored by add-back of microglia to astrocyte-neuron cocultures. Because microglia do not express the classical Pgr, we examined the role of Pgrmc1, which is expressed in microglia in vitro and in vivo. Knockdown by siRNA-Pgrmc1 in microglia before add-back to astrocyte-neuron cocultures suppressed the P4-E2 antagonism of neurite outgrowth. Conditioned media from microglia restored the P4-E2 activity, but only if microglia were activated by lipopolysaccharide or by wounding. Moreover, the microglial activation was blocked by Pgmrc1-siRNA knockdown. These findings explain why nonwounded cultures without microglial activation lack P4 antagonism of E2-induced neurite outgrowth. We suggest that microglial activation may influence brain responses to exogenous P4, which is a prospective therapy in traumatic brain injury. (Endocrinology 154: 2468 -2480, 2013) C ross talk between estradiol (E2) and progesterone (P4) operates throughout the female reproductive system in cycles of E2-dependent cell growth and P4-dependent cell regression. However, little is known of the brain cell interactions that enable "P4-E2 antagonism" in synaptic plasticity. In neuronal responses to injury that involve P4-E2 antagonism, we describe a novel role of microglial activation that is mediated by progesterone receptor (Pgr) membrane component 1 (Pgrmc1)/S2R, a nonclassical Pgr of emerging significance to brain neuronal functions and innate immunity.In the hippocampus, synaptic remodeling during the rat estrous cycle is driven by serial elevations of E2 and P4 (1). Neuronal sprouting in response to axotomy is also modulated by P4-E2 antagonism. In an adult rat model of entorhinal cortex lesions that axotomize the perforant pathway to the hippocampus, the ensuing compensatory neurite outgrowth into the dentate gyrus molecular layer was stimulated by E2 and blocked by concurrent administration of E2ϩP4 (2). Astrocyte and microglial activation in the deafferented zone was correspondingly modulated by E2 and P4. An unexpected role of microglia in P4-E2 antagonism of neurite outgrowth was identified with the "wounding-in-a-dish" model of ax...

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Plasminogen activator inhibitor type 1 regulates microglial motility and phagocytic activity

Cited by 87 publications

References 107 publications

Role of Lipocalin-2-Chemokine Axis in the Development of Neuropathic Pain following Peripheral Nerve Injury

Role of Lipocalin-2-Chemokine Axis in the Development of Neuropathic Pain following Peripheral Nerve Injury

Obesity and dementia: Adipokines interact with the brain

Progesterone Antagonism of Neurite Outgrowth Depends on Microglial Activation via Pgrmc1/S2R

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