Tenascin-C: A novel mediator of hepatic ischemia and reperfusion injury

Kuriyama, Naohisa; Duarte, Sergio; Hamada, Takashi; Busuttil, Ronald W.; Coito, Ana J.

doi:10.1002/hep.24639

Cited by 46 publications

(52 citation statements)

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“…Expression levels of each protein are expressed as a ratio of β-tubulin levels for normalization and as mean±standard deviation. P value, ANOVA MAPK-independent pathways [34], while TNC may stimulate synthesis of IL-1β [35]. The positive feedback mechanisms between TNC and IL-1β may cause post-SAH BBB disruption.…”

Section: Discussionmentioning

confidence: 99%

Anti-Vascular Endothelial Growth Factor Treatment Suppresses Early Brain Injury After Subarachnoid Hemorrhage in Mice

et al. 2015

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The role of vascular endothelial growth factor (VEGF) in early brain injury (EBI) after subarachnoid hemorrhage (SAH) remains unclear. The aim of this study was to investigate effects of anti-VEGF therapy on EBI after SAH. C57BL/6 male mice underwent sham or filament perforation SAH modeling, and vehicle or two dosages (0.2 and 1 μg) of anti-VEGF antibody were randomly administrated by an intracerebroventricular injection. Neuroscore, brain water content, immunoglobulin G staining, and Western blotting were performed to evaluate EBI at 24-48 h. To confirm the role of VEGF, anti-VEGF receptor (VEGFR)-2 (a major receptor of VEGF) antibody was intracerebroventricularly administered and the effects on EBI were evaluated at 24 h. A higher dose, but not a lower dose, of anti-VEGF antibody significantly ameliorated post-SAH neurological impairments and brain edema at 24-48 h post-SAH. Post-SAH blood-brain barrier disruption was also inhibited by anti-VEGF antibody. The protective effects of anti-VEGF antibody were associated with the inhibition of post-SAH induction of VEGF, VEGFR-2, phosphorylated VEGFR-2, interleukin-1β and a matricellular protein tenascin-C (TNC). Anti-VEGFR-2 antibody also suppressed post-SAH neurological impairments and brain edema associated with VEGFR-2 inactivation and TNC downregulation. These findings demonstrated that VEGF causes post-SAH EBI via VEGFR-2 and TNC and that anti-VEGF therapy is effective for post-SAH EBI.

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Section: Discussionmentioning

confidence: 99%

Anti-Vascular Endothelial Growth Factor Treatment Suppresses Early Brain Injury After Subarachnoid Hemorrhage in Mice

et al. 2015

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“…12,14 In addition, TNKO mice showed a marked decrease in expressions of inflammatory cytokines and MMP-9 after hepatic ischemia and reperfusion. 15 This study first demonstrated the link between TNC induction and MMP-9 upregulation or BBB disruption in the brain following SAH by using TNKO mice and exogenous TNC treatment. Although it remains unknown how TNC upregulates MMP-9, TNC induces MAPKs, 8,15 which are known to upregulate MMP-9.…”

Section: Discussionmentioning

confidence: 99%

“…15 This study first demonstrated the link between TNC induction and MMP-9 upregulation or BBB disruption in the brain following SAH by using TNKO mice and exogenous TNC treatment. Although it remains unknown how TNC upregulates MMP-9, TNC induces MAPKs, 8,15 which are known to upregulate MMP-9. 4 Because this study also demonstrated that TNC regulated MAPK activation in brain capillary endothelial cells, it may be reasonable to consider that TNC induces MMP-9 and causes BBB disruption in mice with SAH via MAPK activation.…”

Section: Discussionmentioning

confidence: 99%

“…Neurological scores (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) were assessed by summing 6 test scores (spontaneous activity; spontaneous movement of 4 limbs; forepaw outstretching; climbing; body proprioception; and response to whisker stimulation), as previously described. 8 A beam balance test investigated the animal's ability to walk on a narrow wooden beam for 60 seconds: 4 points, walking ≥ 20 cm; 3 points, walking ≥ 10 cm but < 20 cm; 2 points, walking ≥ 10 cm but falling; 1 point, walking < 10 cm; and 0 points, falling while walking < 10 cm.…”

Section: Neurobehavioral Testmentioning

confidence: 99%

“…Accumulating evidence suggests a role for matrix metalloproteinase (MMP)-9 in the early disruption of the BBB following SAH, 20 and TNC upregulates MMP-9 expression in certain situations. 12,14,15 Therefore, in the present study, we used TNKO mice to evaluate the role of TNC induction in brain edema formation and BBB disruption following SAH.…”

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confidence: 99%

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Deficiency of tenascin-C and attenuation of blood-brain barrier disruption following experimental subarachnoid hemorrhage in mice

Fujimoto¹,

Shiba²,

Kawakita³

et al. 2016

JNS

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A neurysmAl subarachnoid hemorrhage (SAH) is one of the most life-threatening cerebrovascular disorders, with high mortality and morbidity rates. 26,33 Delayed cerebral ischemia (DCI) remains the most important cause of morbidity and mortality in those patients who survive the initial bleeding. 20 Recent studies have reported that early brain injury (EBI), as well as cerebral vasospasm, is a major cause of DCI following SAH. 20EBI occurs before the onset of cerebral vasospasm and may cause DCI with no significant vasospasm. 3 Brain edema, which results mainly from blood-brain barrier (BBB) disruption, 18 plays an important role in the pathological abbreviatioNs BBB = blood-brain barrier; DCI = delayed cerebral ischemia; EBI = early brain injury; ERK = extracellular signal-regulated kinase; ICA = internal carotid artery; JNK = c-Jun N-terminal kinase; MAPK = mitogen-activated protein kinase; MMP = matrix metalloproteinase; PBS = phosphate-buffered saline; PDGF = plateletderived growth factor; SAH = subarachnoid hemorrhage; TNC = tenascin-C; TNKO = TNC knockout; WT = wild-type; ZO = zona occludens. obJective Tenascin-C (TNC), a matricellular protein, is induced in the brain following subarachnoid hemorrhage (SAH). The authors investigated if TNC causes brain edema and blood-brain barrier (BBB) disruption following experimental SAH. methods C57BL/6 wild-type (WT) or TNC knockout (TNKO) mice were subjected to SAH by endovascular puncture. Ninety-seven mice were randomly allocated to WT sham-operated (n = 16), TNKO sham-operated (n = 16), WT SAH (n = 34), and TNKO SAH (n = 31) groups. Mice were examined by means of neuroscore and brain water content 24-48 hours post-SAH; and Evans blue dye extravasation and Western blotting of TNC, matrix metalloproteinase (MMP)-9, and zona occludens (ZO)-1 at 24 hours post-SAH. As a separate study, 16 mice were randomized to WT sham-operated, TNKO sham-operated, WT SAH, and TNKO SAH groups (n = 4 in each group), and activation of mitogen-activated protein kinases (MAPKs) was immunohistochemically evaluated at 24 hours post-SAH. Moreover, 40 TNKO mice randomly received an intracerebroventricular injection of TNC or phosphate-buffered saline, and effects of exogenous TNC on brain edema and BBB disruption following SAH were studied. results Deficiency of endogenous TNC prevented neurological impairments, brain edema formation, and BBB disruption following SAH; it was also associated with the inhibition of both MMP-9 induction and ZO-1 degradation. Endogenous TNC deficiency also inhibited post-SAH MAPK activation in brain capillary endothelial cells. Exogenous TNC treatment abolished the neuroprotective effects shown in TNKO mice with SAH. coNclusioNs Tenascin-C may be an important mediator in the development of brain edema and BBB disruption following SAH, mechanisms for which may involve MAPK-mediated MMP-9 induction and ZO-1 degradation. TNC could be a molecular target against which to develop new therapies for SAH-induced brain injuries.

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Involvement of the extracellular matrix proteins periostin and tenascin C in nasal polyp remodeling by regulating the expression of MMPs

Wang

Zhang

et al. 2021

Clinical & Translational All

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Background Tissue remodeling caused by increased MMPs is involved in the pathogenesis of chronic rhinosinusitis with nasal polyposis (CRSwNP). We previously found higher levels of periostin and tenascin C in CRSwNPs, but whether they are associated with the dysregulation of MMPs is unknown. Therefore, the present study aimed to investigate the regulatory roles of these two ECM proteins in the expression of MMPs in nasal polyps. Methods The concentrations of MMP‐2, MMP‐3, MMP‐7, MMP‐8, MMP‐9, MMP‐12, MMP‐13, TIMP‐1, TIMP‐2, TIMP‐3, TIMP‐4, periostin, and tenascin C in tissue homogenates of 51 patients with chronic rhinosinusitis with and without nasal polyps and 15 control subjects were measured and were analyzed by adjusted logistic regression and spearman correlation test. Primary human nasal polyp fibroblasts and epithelial cells were stimulated ex vivo with periostin and tenascin C and the gene expression of MMPs and TIMPs was determined by means of real‐time PCR. Results The protein levels of MMP‐3, MMP‐7, MMP‐8, MMP‐9, TIMP‐1, TIMP‐2, periostin, and tenascin C were significantly higher in patients with CRSwNPs than in healthy control subjects. The adjusted logistic regression analyses showed that MMP‐3, MMP‐7, MMP‐8, MMP‐9, TIMP‐2, periostin, and tenascin C were related to the occurrence of CRSwNP. Spearman correlation test showed periostin was positively correlated with MMP‐3 and TIMP‐2, and tenascin C was positively correlated with MMP‐3, MMP‐7, MMP‐8, MMP‐9, and TIMP‐2. Periostin stimulated the gene expression of MMP‐3, MMP‐7, MMP‐8, and MMP‐9 in fibroblasts and MMP‐9 in epithelial cells ex vivo. Tenascin C stimulated the expression of MMP‐3, MMP‐7, MMP‐8, and MMP‐9 in epithelial cells. The expression of TIMPs in fibroblasts and epithelial cells was affected by neither periostin nor tenascin C. Conclusions Periostin and tenascin C might be involved in the remodeling of nasal polyps by regulating the expression of different MMPs in epithelial cells and fibroblasts. Our findings have the potential to identify key factors of tissue remodeling in CRSwNPs.

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Tenascin-C: A novel mediator of hepatic ischemia and reperfusion injury

Cited by 46 publications

References 50 publications

Anti-Vascular Endothelial Growth Factor Treatment Suppresses Early Brain Injury After Subarachnoid Hemorrhage in Mice

Anti-Vascular Endothelial Growth Factor Treatment Suppresses Early Brain Injury After Subarachnoid Hemorrhage in Mice

Deficiency of tenascin-C and attenuation of blood-brain barrier disruption following experimental subarachnoid hemorrhage in mice

Involvement of the extracellular matrix proteins periostin and tenascin C in nasal polyp remodeling by regulating the expression of MMPs

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