The significance of matrix metalloproteinase (MMP)-2 and MMP-9 in the ischemic stroke

Kurzepa, Jacek; Kurzepa, Joanna; Golab, Piotr; Czerska, Sara; Bielewicz, Joanna

doi:10.3109/00207454.2013.872102

Cited by 114 publications

(89 citation statements)

References 87 publications

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“…The characteristics of miRNA binding sites in mRNA of ZFHX3 gene and its orthologs S ome genes have been identified in stroke and they are considered as candidates to determine various subtypes of stroke (Mineharu et al, 2006;Kurzepa et al, 2014;Inose et al, 2015;Wu et al, 2017). These include the ZFHX3 gene encoding the transcription factor involved in the regulation of expression of many genes.…”

mentioning

confidence: 99%

The Characteristics of Mirna Binding Sites in Mrna of Zfhx3 Gene and Its Orthologs

Kondybaeva¹,

Акимниязова²,

Kamenova³

et al. 2018

Vestn. VOGiS

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Transcription factor gene ZFHX3 is one of the candidate genes involved in stroke development. The ZFHX3 protein contains oligopeptides encoded by trinucleotide repeats (TNRs). TNR variability is considered to be one of the causes of the disease, but their biological function has not yet been established. We assume that TNRs are the binding sites of miRNA to mRNA and are involved in regulation of ZFHX3 gene expression. The characteristics of miRNA–mRNA interaction were determined using MirTarget software. It has been shown that the first TNR in mRNA of the human ZFHX3 gene consists of the seven consecutive miR-12-32603-3p binding encoding polyGlu. The ZFHX3 protein of human polyGlu contains 30 Glu. In the orthologous proteins of 36 animal species the length of polyGlu varied from 27 Glu to 33 Glu. Negatively charged polyGlu of the ZFHX3 transcription factor probably interacted with positive DNA-binding proteins. The following mRNA region of the ZFHX3 gene contained the binding sites for miR-17-39416-3p, miR-5-15733-3p, miR-9-20317-3 encoding polyAla by 15 Ala lengths. In the 33 ZFHX3 orthologous proteins polyAla had the same length. The mRNA region of the human ZFHX3 gene with binding polysite of miR-1322-3p encoded polyGln consisting of 19 Gln. In the 41 orthologs of the ZFHX3 protein the length of polyGln varied from seven Gln to 23 Gln. The binding sites of miR-2-6184-3p, miR-5-14114-5p and miR-19-43437-5p were located with overlapping nucleotides sequences, and encode polyPro. In ZFHX3 human polyPro consisted of 12 Pro. In the orthologs, polyPro contained from 10 Pro to 14 Pro. The binding sites of miR-17-39416-3p, miR-9-20317-3p, miR-1-1819-3p, miR-5-15733-3p, miR-6-17815-3p, miR-18-39953-5p, miR-26862-5p, miR-1260b and miR-X-48174-3p in human ZFHX3 encoded polyGly by 22 Gly length. In the 28 orthologs of ZFHX3 the length of polyGly decreased to 11 Gly. The TNR regions could simultaneously bind several miRNAs, which increased the dependence of gene expression on miRNA. The oligopeptides encoded by the binding polysites of miRNA in mRNA in the orthologous ZFHX3 proteins were flanked by conserved oligopeptides.

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mentioning

confidence: 99%

The Characteristics of Mirna Binding Sites in Mrna of Zfhx3 Gene and Its Orthologs

Kondybaeva¹,

Акимниязова²,

Kamenova³

et al. 2018

Vestn. VOGiS

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“…A reduction in MMP-2 and MMP-9 expression was observed following RB-222 treatment. It has been reported that the instant elevation of MMPs in acute ischemia-induced brain injury is involved in the digestion of the endothelial basal lamina and the triggering of secondary injury, including brain edema in acute stroke (8). The inhibition of MMPs promotes BBB restoration and neurovascular remodeling following stroke (9).…”

Section: Discussionmentioning

confidence: 99%

“…Numerous proinflammatory agents that are trigged by ischemia can activate MMP expression immediately after a stroke (8). In acute ischemia, MMP-2 and MMP-9 in particular, mediated degradation of tight junction proteins (TJPs) in the BBB (9).…”

Section: Introductionmentioning

confidence: 99%

“…In acute ischemia, MMP-2 and MMP-9 in particular, mediated degradation of tight junction proteins (TJPs) in the BBB (9). It has been demonstrated that MMP inhibition is an important therapeutic strategy to reduce brain damage during acute stroke (8). Several studies have suggested a strong relationship between the induction of MMP-2 and MMP-9 and brain edema following cerebral ischemic injury (10–12), indicating that MMP-2 and MMP-9 may be important targets to prevent edema complications following cerebral ischemia.…”

Section: Introductionmentioning

confidence: 99%

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Early VEGF inhibition attenuates blood-brain barrier disruption in ischemic rat brains by regulating the expression of MMPs

Zhang

Gao

et al. 2016

Molecular Medicine Reports

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Vascular endothelial growth factor (VEGF) inhibition has been demonstrated to be an effective strategy in preserving the integrity of the blood-brain barrier (BBB) in patients with acute ischemic stroke. Loss of the BBB is the key event associated with morbidity and mortality in these patients. However, the underlying mechanisms remain poorly understood. In the present study, the effects of VEGF inhibition and the possible mechanism that underlies acute cerebral ischemia in rats was investigated. Following the induction of transient middle cerebral artery occlusion for a 90-min period, either an anti-VEGF neutralizing antibody (RB-222; 5 or 10 µg), or IgG (control), was administered by intracerebroventricular injection at 1 h following reperfusion. Functional outcomes, BBB leakage, brain edema, microvessel numbers and the relative protein levels of VEGF, matrix metalloproteinase (MMP)-2, MMP-9, occludin and collagen-IV were then determined using neurological assessments, Evans Blue staining, brain water content, CD31 staining and western blotting. Treatment with RB-222 at a dose of 5 and 10 µg significantly improved neurological functional outcomes and diminished infarct size, BBB leakage and brain edema compared with the MCAO and IgG groups at 24 h following reperfusion; 10 µg RB-222 was more effective than a 5 µg dose of the antibody. In addition, RB-222 reduced the number of immature microvessels, which subsequently attenuated BBB permeability. RB-222 significantly repressed VEGF expression as well as decreased MMP-2 and MMP-9 expression. However, it enhanced occludin and collagen-IV levels in the ischemic rat brain compared with the MCAO and IgG groups. Taken together, the results indicate that early inhibition of VEGF may have significant potential against cerebral ischemia, partly by regulating the expression of MMPs.

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“…Furthermore, due to the digestion of collagen type IV (a component of basal membranes), the transfer of leukocytes across the endothelium can be facilitated. 17 We determined that extracranial and intracranial ICA plaques, female gender had effect on MMP-2 levels. The present study also compared patients according to the presence of intracranial carotid DA, but there were no significant differences in terms of MMP levels or other parameters.…”

Section: Article In Pressmentioning

confidence: 99%

Matrix Metalloproteinase Levels in Cervical and Intracranial Carotid Dolichoarteriopathies

Arslan

Pekçevik

et al. 2016

Journal of Stroke and Cerebrovascular Diseases

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The significance of matrix metalloproteinase (MMP)-2 and MMP-9 in the ischemic stroke

Cited by 114 publications

References 87 publications

The Characteristics of Mirna Binding Sites in Mrna of Zfhx3 Gene and Its Orthologs

The Characteristics of Mirna Binding Sites in Mrna of Zfhx3 Gene and Its Orthologs

Early VEGF inhibition attenuates blood-brain barrier disruption in ischemic rat brains by regulating the expression of MMPs

Matrix Metalloproteinase Levels in Cervical and Intracranial Carotid Dolichoarteriopathies

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