کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
7279352 | 1473897 | 2018 | 38 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Notch signaling is impaired during inflammation in a Lunatic Fringe-dependent manner
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کلمات کلیدی
qRT-PCRbarrier resistancelFngPofut1quantitative reverse transcriptase PCRZO-1BECsTEERECISDAPTFCSAPCHEKshRNAGlcNAcPBSNTCMFINGSDMSO - DMSON-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester - N- [N- (3،5-difluorophenacetyl) -L-alanyl] -S-phenylglycine t-butyl estershort hairpin RNA - RNA موی سر کوتاهallophycocyanin - آلوفوکسیانینTight junction - اتصال تنگinflammation - التهاب( توروم) Lunatic fringe - حاشیه خاموشstandard error of the mean - خطای استاندارد میانگینCNS - دستگاه عصبی مرکزیDimethyl sulfoxide - دیمتیل سولفواکسیدBBB - سد خونی مغزیnormal goat serum - سرم طبیعی بزfetal calf serum - سرم گوساله جنینbrain endothelial cells - سلول های اندوتلیال مغزیElectric cell-substrate impedance sensing - سنجش امپدانس الکتریکی سلول-سوبستراcentral nervous system - سیستم عصبی مرکزیVascular endothelial growth factor - فاکتور رشد اندوتلیال عروقیVascular Endothelial Growth Factor (VEGF) - فاکتور رشد اندوتلیال عروقی (VEGF)Blood-brain barrier - مانع خون مغزیVasculature - مجاورPhosphate-buffered saline - محلول نمک فسفات با خاصیت بافریSEM - مدل معادلات ساختاری / میکروسکوپ الکترونی روبشیtransendothelial electrical resistance - مقاومت الکتریکی transendothelialMultiple sclerosis - مولتیپل اسکلروزیس(ام اس)mean fluorescence intensity - میانگین شدت فلورسانسNotch signaling - نشانه گیریZonula occludens-1 - نوار ابزار بسته 1N-acetylglucosamine - نیتستیگلوکوزامینhuman embryonic kidney - کلیه جنین انسانGlycosylation - گلیکوزیله شدن
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ایمونولوژی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The blood-brain barrier (BBB) assures brain homeostasis through the specialized function of brain endothelial cells (BECs). Dysfunction of the BBB due to inflammatory processes is associated with several neurological disorders, including multiple sclerosis (MS). Understanding the mechanisms that underlie these processes may ultimately lead to new therapeutic strategies to restore BBB function, thereby fighting disease progression. In this study, we demonstrate for the first time a critical role of the Notch signaling pathway in the function of the BBB under resting and inflammatory conditions. Inhibition of the Notch signaling, either by a γ-secretase inhibitor or by genetic ablation of endothelial NOTCH, led to BBB dysfunction in vitro as evidenced by reduced transendothelial electrical resistance (TEER), altered localization and loss of endothelial junction molecules and enhanced macromolecular permeability. Inflamed BECs showed impaired Notch signaling as indicated by reduced level of the downstream targets HES-1 and HES-5. Notably, barrier function was further reduced when the Notch signaling was inhibited under inflammatory conditions, suggesting an additive effect of the Notch signaling and inflammation in BECs. In contrast, inducible overexpression of Notch-intracellular domain 1 (NICD1) rescued the detrimental effect caused by inflammation. Furthermore, we provide evidence that inflammation reduced the expression of the glycosyltransferase Lunatic Fringe (LFNG), a known positive regulator of Notch glycosylation and signaling, thereby leading to disrupted barrier function of BECs. Together, our data demonstrate the functional importance of the conserved Notch signaling pathway in control of the brain endothelial barrier and shed light on the role of LFNG in the regulation of Notch glycosylation and signaling in the adult brain vasculature in both health and disease.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain, Behavior, and Immunity - Volume 69, March 2018, Pages 48-56
Journal: Brain, Behavior, and Immunity - Volume 69, March 2018, Pages 48-56
نویسندگان
Claudio Derada Troletti, Melissa A. Lopes Pinheiro, Marc Charabati, Elizabeth Gowing, Bert van het Hof, Susanne M.A. van der Pol, Dirk Geerts, Alexandre Prat, Ruud D. Fontijn, Wendy W. Unger, Helga E. de Vries,