The Rapid Decrease in Astrocyte-Associated Dystroglycan Expression by Focal Cerebral Ischemia is Protease-Dependent

Milner, Richard; Hung, S.; Wang, Xiaoyun; Spatz, Maria; Zoppo, Gregory J. del

doi:10.1038/sj.jcbfm.9600585

Cited by 75 publications

(106 citation statements)

References 41 publications

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“…The presence of the 30 kDa b-DG fragment has been reported under different pathological conditions of the skeletal muscle, such as Duchenne muscular dystrophy, Fukuyama-type congenital dystrophy and sarcoglycanopathy (12). The 30 kDa b-DG fragment was also detected in tissues subjected to ischemic injury (13,14) and in joint tissues from patients affected by osteoarthritis (15); finally, b-DG degradation was also discovered in some forms of epithelial cancerous cells (16). In any case, the 30 kDa b-DG fragment lacks all or part of the b-DG ectodomain, as it can be detected using the monoclonal antibody 43DAG directed against the C-terminus of b-DG.…”

Section: Introductionmentioning

confidence: 76%

Enzymatic processing of β‐dystroglycan recombinant ectodomain by MMP‐9: Identification of the main cleavage site

et al. 2009

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SummaryDystroglycan (DG) is a membrane receptor belonging to the complex of glycoproteins associated to dystrophin. DG is formed by two subunits, a-DG, a highly glycosylated extracellular matrix protein, and b-DG, a transmembrane protein. The two DG subunits interact through the C-terminal domain of a-DG and the N-terminal extracellular domain of b-DG in a noncovalent way. Such interaction is crucial to maintain the integrity of the plasma membrane. In some pathological conditions, the interaction between the two DG subunits may be disrupted by the proteolytic activity of gelatinases (i.e. MMP-9 and/or MMP-2) that removes a portion or the whole b-DG ectodomain producing a 30 kDa truncated form of b-DG. However, the molecular mechanism underlying this event is still unknown. In this study, we carried out proteolysis of the recombinant extracellular domain of b-DG, b-DG(654-750) with human MMP-9, characterizing the catalytic parameters of its cleavage. Furthermore, using a combined approach based on SDS-PAGE, MALDI-TOF and HPLC-ESI-IT mass spectrometry, we were able to identify one main MMP-9 cleavage site that is localized between the amino acids His-715 and Leu-716 of b-DG, and we analysed the proteolytic fragments of b-DG(654-750) produced by MMP-9 enzymatic activity.

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Section: Introductionmentioning

confidence: 76%

Enzymatic processing of β‐dystroglycan recombinant ectodomain by MMP‐9: Identification of the main cleavage site

et al. 2009

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“…Loss of laminin-binding integrin and dystroglycan receptors at the astrocyte-vascular interface occurs in models of ischemia (Wagner et al, 1997;Tagaya et al, 2001;Milner et al, 2008). Astrocytes play a crucial role in maintaining the blood-brain barrier (Abbott et al, 2006), and astrocytes can induce properties of the blood-brain barrier in cultured endothelial cells (Wolburg et al, 1994;Gardner et al, 1997).…”

Section: Laminins Maintain Vascular Stabilitymentioning

confidence: 99%

Laminins containing the β2 and γ3 chains regulate astrocyte migration and angiogenesis in the retina

et al. 2013

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SUMMARYPathologies of retinal blood vessels are among the major causes of blindness worldwide. A key cell type that regulates retinal vascular development is the astrocyte. Generated extrinsically to the retina, astrocytes migrate into the retina through the optic nerve head. Even though there is a strong correlation between astrocyte distribution and retinal vascular development, the factors that guide astrocytes into the retina remain unclear. In this study, we show that astrocytes migrate within a laminin-containing basement membrane -the inner limiting membrane. Genetic deletion of the laminin β2 and γ3 chains affects astrocyte migration and spatial distribution. We show that laminins act as haptotactic factors in vitro in an isoform-specific manner, inducing astrocyte migration and promoting astrocyte differentiation. The addition of exogenous laminins to laminin-null retinal explants rescues astrocyte migration and spatial patterning. Furthermore, we show that the loss of laminins reduces β1 integrin expression in astrocytes. Culturing lamininnull retinal astrocytes on laminin substrates restores focal localization of β1 integrin. Finally, we show that laminins containing β2 and γ3 chains regulate subsequent retinal blood vessel growth and maintain vascular integrity. These in vivo and in vitro studies demonstrate clearly that laminins containing β2 and γ3 chains are indispensable for migration and spatial organization of astrocytes and that they play a crucial role during retinal angiogenesis in vivo. RESEARCH ARTICLELaminins regulate angiogenesis treatment with exogenous laminins rescues astrocyte migration and spatial patterning phenotype ex vivo. Together, these data support the hypothesis that β2-and γ3-containing laminins are important cues in retinal vascular development.

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“…However, during focal ischemia endothelial cell demise is infrequent, suggesting the stability of endothelial cell-matrix adhesion (Tagaya et al, 1997). In contrast, focal ischemia induces detachment of astrocyte end-feet from the basal lamina (Garcia et al, 1971;Milner et al, 2008b;Kwon et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Interendothelial Claudin-5 Expression Depends on Cerebral Endothelial Cell–Matrix Adhesion by β₁-Integrins

Osada

Kanazawa

et al. 2011

J Cereb Blood Flow Metab

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128

120

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The hypothesis tested by these studies states that in addition to interendothelial cell tight junction proteins, matrix adhesion by b 1 -integrin receptors expressed by endothelial cells have an important role in maintaining the cerebral microvessel permeability barrier. Primary brain endothelial cells from C57 BL/6 mice were incubated with b 1 -integrin function-blocking antibody (Ha2/5) or isotype control and the impacts on claudin-5 expression and microvessel permeability were quantified. Both flow cytometry and immunofluorescence studies demonstrated that the interendothelial claudin-5 expression by confluent endothelial cells was significantly decreased in a time-dependent manner by Ha2/5 exposure relative to isotype. Furthermore, to assess the barrier properties, transendothelial electrical resistance and permeability measurements of the monolayer, and stereotaxic injection into the striatum of mice were performed. Ha2/5 incubation reduced the resistance of endothelial cell monolayers significantly, and significantly increased permeability to 40 and 150 kDa dextrans. Ha2/5 injection into mouse striatum produced significantly greater IgG extravasation than the isotype or the control injections. This study demonstrates that blockade of b 1 -integrin function changes interendothelial claudin-5 expression and increases microvessel permeability. Hence, endothelial cell-matrix interactions via b 1 -integrin directly affect interendothelial cell tight junction claudin-5 expression and brain microvascular permeability.

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The Rapid Decrease in Astrocyte-Associated Dystroglycan Expression by Focal Cerebral Ischemia is Protease-Dependent

Cited by 75 publications

References 41 publications

Enzymatic processing of β‐dystroglycan recombinant ectodomain by MMP‐9: Identification of the main cleavage site

Enzymatic processing of β‐dystroglycan recombinant ectodomain by MMP‐9: Identification of the main cleavage site

Laminins containing the β2 and γ3 chains regulate astrocyte migration and angiogenesis in the retina

Interendothelial Claudin-5 Expression Depends on Cerebral Endothelial Cell–Matrix Adhesion by β₁-Integrins

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The Rapid Decrease in Astrocyte-Associated Dystroglycan Expression by Focal Cerebral Ischemia is Protease-Dependent

Cited by 75 publications

References 41 publications

Enzymatic processing of β‐dystroglycan recombinant ectodomain by MMP‐9: Identification of the main cleavage site

Enzymatic processing of β‐dystroglycan recombinant ectodomain by MMP‐9: Identification of the main cleavage site

Laminins containing the β2 and γ3 chains regulate astrocyte migration and angiogenesis in the retina

Interendothelial Claudin-5 Expression Depends on Cerebral Endothelial Cell–Matrix Adhesion by β1-Integrins

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Interendothelial Claudin-5 Expression Depends on Cerebral Endothelial Cell–Matrix Adhesion by β₁-Integrins