کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10913932 | 1088655 | 2009 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Perlecan regulates developmental angiogenesis by modulating the VEGF-VEGFR2 axis
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کلمات کلیدی
HSPGPDGFPLCγ1TGFISVGAGHUVECVEGFR2HCAECFGFDICSIVintersegmental vesseldorsal aorta - آئورت پشتیAngiogenesis - آنژیوژنزtransforming growth factor - تبدیل فاکتور رشدHedgehog - جوجهتیغی، خارپشتShh - خیرHuman coronary artery endothelial cell - سلول اندوتلیال عروق کرونر انسانیHuman umbilical vein endothelial cell - سلول اندوتلیالی ورید ناقل انسانیEndothelial cell - سلول های اندوتلیالsonic hedgehog - صدای جیر جیرVascular endothelial growth factor - فاکتور رشد اندوتلیال عروقیVascular Endothelial Growth Factor (VEGF) - فاکتور رشد اندوتلیال عروقی (VEGF)platelet derived growth factor - فاکتور رشد حاصل از پلاکتfibroblast growth factor - فاکتور رشد فیبروبلاستHeparan sulfate - هپاران سولفاتHeparan sulfate proteoglycan - هپارین سولفات پروتئگلیکانposterior cardinal vein - ورید قلبی خلفیperlecan - پرلکانPCV - پی وی سیdifferential interference contrast - کنتراست تداخل دیفرانسیلGlycosaminoglycan - گلیکوزآمینوگلیکانZebrafish - گورخرماهیVEGF receptor - گیرنده VEGFvascular endothelial growth factor receptor 2 - گیرنده فاکتور رشد اندوتلیال عروقی 2
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Using the zebrafish, we previously identified a central function for perlecan during angiogenic blood vessel development. Here, we explored the nature of perlecan function during developmental angiogenesis. A close examination of individual endothelial cell behavior revealed that perlecan is required for proper endothelial cell migration and proliferation. Because these events are largely mediated by VEGF-VEGFR2 signaling, we investigated the relationship between perlecan and the VEGF pathway. We discovered that perlecan knockdown caused an abnormal increase and redistribution of total VEGF-A protein suggesting that perlecan is required for the appropriate localization of VEGF-A. Importantly, we linked perlecan function to the VEGF pathway by efficiently rescuing the perlecan morphant phenotype by microinjecting VEGF-A165 protein or mRNA. Combining the strategic localization of perlecan throughout the vascular basement membrane along with its growth factor-binding ability, we hypothesized a major role for perlecan during the establishment of the VEGF gradient which provides the instructive cues to endothelial cells during angiogenesis. In support of this hypothesis we demonstrated that human perlecan bound in a heparan sulfate-dependent fashion to VEGF-A165. Moreover, perlecan enhanced VEGF mediated VEGFR2 activation of human endothelial cells. Collectively, our results indicate that perlecan coordinates developmental angiogenesis through modulation of VEGF-VEGFR2 signaling events. The identification of angiogenic factors, such as perlecan, and their role in vertebrate development will not only enhance overall understanding of the molecular basis of angiogenesis, but may also provide new insight into angiogenesis-based therapeutic approaches.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Matrix Biology - Volume 28, Issue 5, June 2009, Pages 284-291
Journal: Matrix Biology - Volume 28, Issue 5, June 2009, Pages 284-291
نویسندگان
Jason J. Zoeller, John M. Whitelock, Renato V. Iozzo,