The expression of osteopontin is increased in vessels with blood–brain barrier impairment

Iwanaga, Yasuyuki; Ueno, Mai; Ueki, Masaaki; Huang, Cheng‐Long; Tomita, Shuhei; Okamoto, Yasuo; Ogawa, Tomoko; Ueda, Nobufumi; Maekawa, Nobuhiro; Sakamoto, Haruhiko

doi:10.1111/j.1365-2990.2007.00877.x

Cited by 32 publications

(34 citation statements)

References 34 publications

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“…The protein has been extensively studied in multiple sclerosis, where it appears to be involved, through the ␣ 4 ␤ 1 integrin, in the entry of effector T cells in the brain (41), and through CD44 receptor, in the permanence of T cells at the site of inflammation. Recent information has suggested that the levels of OPN in CSF are not disease specific, but can point to involvement of the CNS or damage to the blood-brain barrier (BBB) (44,45). The levels of OPN in the CSF of S2 HAT patients analyzed in the present study were significantly higher than in S1 patients, suggesting an association between CSF OPN and disease progression.…”

Section: Discussionmentioning

confidence: 37%

Discovery and Verification of Osteopontin and Beta-2-microglobulin as Promising Markers for Staging Human African Trypanosomiasis

Tiberti¹,

Hainard²,

Lejon

et al. 2010

Molecular & Cellular Proteomics

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Human African trypanosomiasis, or sleeping sickness, is a parasitic disease endemic in sub-Saharan Africa, transmitted to humans through the bite of a tsetse fly. The first or hemolymphatic stage of the disease is associated with presence of parasites in the bloodstream, lymphatic system, and body tissues. If patients are left untreated, parasites cross the blood-brain barrier and invade the cerebrospinal fluid and the brain parenchyma, giving rise to the second or meningoencephalitic stage. Stage determination is a crucial step in guiding the choice of treatment, as drugs used for S2 are potentially dangerous. Current staging methods, based on counting white blood cells and demonstrating trypanosomes in cerebrospinal fluid, lack specificity and/or sensitivity. In the present study, we used several proteomic strategies to discover new markers with potential for staging human African trypanosomiasis. Cerebrospinal fluid (CSF) samples were collected from patients infected with Trypanosoma brucei gambiense in the Democratic Republic of Congo. The stage was determined following the guidelines of the national control program. The proteome of the samples was analyzed by two-dimensional gel electrophoresis (n ‫؍‬ 9), and by sixplex tandem mass tag (TMT) isobaric labeling (n ‫؍‬ 6) quantitative mass spectrometry. Overall, 73 proteins were overexpressed in patients presenting the second stage of the disease. Two of these, osteopontin and ␤-2-microglobulin, were confirmed to be potential markers for staging human African trypanosomiasis (HAT) by Western blot and ELISA. The two proteins significantly discriminated between S1 and S2 patients with high sensitivity (68% and 78%, respectively) for 100% specificity, and a combination of both improved the sensitivity to 91%. The levels of osteopontin and ␤-2-microglobulin in CSF of S2 patients (g/ml range), as well as the fold increased concentration in S2 compared with S1 (3.8 and 5.5 respectively) make the two markers good candidates for the development of a test for staging HAT patients. Molecular & Cellular Proteomics 9:2783-2795, 2010.

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Section: Discussionmentioning

confidence: 37%

Discovery and Verification of Osteopontin and Beta-2-microglobulin as Promising Markers for Staging Human African Trypanosomiasis

Tiberti¹,

Hainard²,

Lejon

et al. 2010

Molecular & Cellular Proteomics

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“…14,15 We then examined differences in gene expression between microdissected hippocampal vessels with BBB impairment in SHRSP and those without the impairment in Wistar Kyoto (WKY) rats using a microarray assay and reported that the expression of osteopontin, a matricellular protein, was increased in BBB-damaged vessels in hypertensive SHRSP compared with that in vessels without BBB impairment in WKY rats. 16 The study also indicated that the immunoreactivity of osteopontin was present in perivascular ED1-positive macrophage/microglial cells and suggested the possibility that osteopontin might act as an inducible modulator of vascular remodeling, which likely restored BBB function in the damaged blood vessels. In addition, we recently reported 17 that the expression of P-glycoprotein, a representative efflux transporter in the brain vessels, was increased in vessels with BBB impairment in the hippocampus of SHRSP.…”

Section: Introductionmentioning

confidence: 76%

“…In addition, the results in the microarray assay also indicated that the expression of transforming growth factor-b receptor II was increased in the hippocampal samples of SHRSP, compared with that in the samples of WKY rats. 16 It is known that transforming growth factor-b enhances MMP-13 expression. 35,36 The increased expression of MMP-13 together with transforming growth factor-b receptor II in the BBB-damaged vessels of SHRSP is compatible with these findings reported earlier.…”

Section: Discussionmentioning

confidence: 99%

“…The earlier study 4 also showed that collagen deposits were occasionally seen in the BBB-damaged vessels. In addition, Iwanaga et al 16 microdissected vascular samples from the hippocampus of SHRSP and WKY rats and examined the difference in gene expression between the vascular samples with BBB impairment of SHRSP and those without impairment of WKY, using a microarray assay. Accordingly, Increased MMP-13 expression in BBB-damaged vessel M Ueno et al osteopontin expression was increased in BBB-damaged hippocampal vessels in SHRSP, compared with hippocampal vessels without the BBB impairment in WKY rats.…”

Section: Discussionmentioning

confidence: 99%

“…30 The PCR cycling conditions for all samples were as follows: 501C, 2 min for AmpErase UNG activation; 951C, 10 min for AmpliTaq Gold activation; and 50 cycles for melting (951C, 15 s) and annealing/extension (601C, 1 min) steps. 16,31 Each sample was run in duplicate, and each PCR experiment included two nontemplate control wells. The comparative threshold cycle method (Applied Biosystems) was used to calculate gene expression in each sample relative to the value observed in control samples using GAPDH as a control for normalization among samples.…”

Section: Real-time Quantitative Rt-pcrmentioning

confidence: 99%

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The expression of matrix metalloproteinase-13 is increased in vessels with blood–brain barrier impairment in a stroke-prone hypertensive model

Ueno

Nishiyama

et al. 2009

Hypertens Res

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We previously reported that the blood-brain barrier (BBB) function was deteriorated in vessels located in the hippocampus, but not the cerebral cortex, in 3-month-old stroke-prone spontaneously hypertensive rats (SHRSP). Recently published data suggest that matrix metalloproteinase (MMP)-2 and MMP-9 play a critical role in the BBB disruption in stroke or cerebral ischemia. In this study, we examined gene and protein expressions of MMPs in the BBB-damaged hippocampal vessels of 3-month-old SHRSP, in the cerebral cortical vessels without BBB damage of SHRSP, and in the hippocampal and cerebral cortical ones without BBB damage of 3-month-old Wistar Kyoto (WKY) rats. The expressions of MMPs were examined by real-time quantitative reverse transcriptase-PCR (RT-PCR), western blotting and immunohistochemical techniques. The gene and protein expressions of MMP-13 were significantly increased in the hippocampal samples of SHRSP compared with samples without BBB damage, such as cerebral cortical samples of SHRSP or hippocampal samples of WKY. Immunostaining of MMP-13 was seen in the cytoplasm of ED-1-positive perivascular cells in both rats and was colocalized with those of type IV collagen or osteopontin. The type IV collagen was also localized in the basement membrane. These findings indicate that the expression of MMP-13 is increased in BBB-damaged hippocampal vessels in hypertensive SHRSP compared with vessels without BBB impairment in normotensive WKY rats and may be involved in vascular remodeling. Keywords: blood-brain barrier; MMP-13; SHRSP INTRODUCTION A causative role of blood-brain barrier (BBB) impairment is suggested in the pathogenesis of vascular dementia with leakage of serum components from small vessels leading to neuronal and glial damage. 1 To clarify the roles of BBB impairment in vascular dementia, we have examined BBB function in various conditions related to vascular dementia, such as hypertension, acute ischemia with reperfusion, chronic cerebral hypoperfusion and aging with or without memory deficits. [2][3][4] Consequently, among these animal models, the most localized BBB impairment was clearly seen in the hippocampus, but not the cerebral cortex, of 3-month-old spontaneously hypertensive rats (SHR), especially of 3-month-old stroke-prone SHR (SHRSP), 4 which were established by Okamoto and Aoki 5 and are described in detail elsewhere. 6,7 It is known that the neuronal loss occurs with a reduction of gray matter volume in the CA1 subfield and dentate gyrus of the hippocampus in SHR at the age of 6 months or order, indicating that SHR can be a good animal model of vascular

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Acute intranasal osteopontin treatment in male rats following TBI increases the number of activated microglia but does not alter lesion characteristics

Jullienne

Hamer

Haddad

et al. 2019

J of Neuroscience Research

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Intranasal recombinant osteopontin (OPN) has been shown to be neuroprotective in different models of acquired brain injury but has never been tested after traumatic brain injury (TBI). We used a model of moderate-to-severe controlled cortical impact in male adult Sprague Dawley rats and tested our hypothesis that OPN treatment would improve neurological outcomes, lesion and brain tissue characteristics, neuroinflammation, and vascular characteristics at 1 day post-injury. Intranasal OPN administered 1 hr after the TBI did not improve neurological score, lesion volumes, blood-brain barrier, or vascular characteristics. When assessing neuroinflammation, we did not observe any effect of OPN on the astrocyte reactivity but discovered an increased number of activated microglia within the ipsilateral hemisphere. Moreover, we found a correlation between edema and heme oxygenase-1 (HO-1) expression which was decreased in OPN-treated animals, suggesting an effect of OPN on the HO-1 response to injury. Thus, OPN may increase or accelerate the microglial response after TBI, and early response of HO-1 in modulating edema formation may limit the secondary consequences of TBI at later time points. Additional experiments and at longer time points are needed to determine if intranasal OPN could potentially be used as a treatment after TBI where it might be beneficial by activating protective signaling pathways. K E Y W O R D S controlled cortical impact, edema, extracellular matrix protein, Heme oxygenase-1, microglial activation, T2 mapping S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section at the end of the article. Supplementary Table S1. Brain regions excluded from T2 values analysis Transparent Science Questionnaire for Authors. How to cite this article: JullienneA, HamerM, HaddadE, et al. Acute intranasal osteopontin treatment in male rats following TBI increases the number of activated microglia but does not alter lesion characteristics. J Neuro Res. 2020;98:141-154.

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The expression of osteopontin is increased in vessels with blood–brain barrier impairment

Abstract: These findings indicate that the expression of osteopontin is increased in BBB-damaged vessels in hypertensive SHRSP compared with that in vessels without BBB impairment in WKY rats, suggesting a role for osteopontin in BBB function.

Cited by 32 publications

References 34 publications

Discovery and Verification of Osteopontin and Beta-2-microglobulin as Promising Markers for Staging Human African Trypanosomiasis

Discovery and Verification of Osteopontin and Beta-2-microglobulin as Promising Markers for Staging Human African Trypanosomiasis

The expression of matrix metalloproteinase-13 is increased in vessels with blood–brain barrier impairment in a stroke-prone hypertensive model

Acute intranasal osteopontin treatment in male rats following TBI increases the number of activated microglia but does not alter lesion characteristics

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