کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10801958 | 1055649 | 2015 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Syndecan-4 ectodomain evokes mobilization of podocyte TRPC6 channels and their associated pathways: An essential role for integrin signaling
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کلمات کلیدی
CilengitideTRPC6ADAM17GBMOAGNFATc1Syndecan-4Nuclear factor of activated T-cells cytoplasmic 1FSGSCGTRhoGAPTNF1-Oleoyl-2-acetyl-sn-glycerolTIMP-3SDC4ROS - ROSPuromycin aminonucleoside - آمینونوکلئوزید پوموایسینAngiotensin II - آنژیوتانسین دوinflammation - التهاب( توروم) CSA - ایالات مؤتلفهٔ آمریکاA disintegrin and metalloproteinase 17 - تخریب و متالوپروتئیناز 17Oxidative stress - تنش اکسیداتیوAng II - دومdiacylglycerol - دیسیل گلیسیرینDAG - روزTempol - سریعCyclosporine A - سیکلوسپورینAglomerular basement membrane - غشاء زیر بغل گلومرولیtumor necrosis factor - فاکتور نکروز تومورPAN - ماهی تابهMetalloproteinase - متالوپروتئیناز Tissue inhibitor of metalloproteinase-3 - مهارکننده های متالوپروتئیناز-3Proteoglycan - پروتئوگلیکانCalcium - کلسیمfocal and segmental glomerulosclerosis - گلومرول اسکلروز مرکزی و سگمنتالReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
PodocyteTRPC6 channels have been implicated in glomerular diseases. Syndecan-4 (Sdc4) is a membrane proteoglycan that can be cleaved to release a soluble ectodomain capable of paracrine and autocrine signaling. We have confirmed that overexpression of Sdc4 core protein increases surface abundance of TRPC6 channels in cultured podocytes, whereas Sdc4 knockdown has the opposite effect. Exposure to soluble Sdc4 ectodomain also increased the surface abundance of TRPC6, and increased cationic currents evoked by a diacylglycerol analog in podocytes. Sdc4 ectodomain increased generation of reactive oxygen species (ROS), reduced activation of RhoA, increased activation of Rac1, increased nuclear abundance of NFATc1, and increased total β3-integrin. The effects of Sdc4 ectodomain on cell-surface TRPC6 were blocked by the ROS quencher TEMPOL, and by the Rac1 inhibitor NSC-23766, but were not blocked by inhibition of calcineurin-NFATc1 signaling. The Sdc4 core protein co-immunoprecipitates with β3-integrin in cultured podocytes. Moreover, effects of Sdc4 ectodomain on TRPC6, ROS generation, Rac1 and RhoA modulation, and NFATc1 activation were blocked by cilengitide, a selective inhibitor of outside-in signaling through αv-containing integrins. Exposure to TNF, or serum from three patients with recurrent FSGS in relapse, increased shedding of podocyte Sdc4 ectodomains into the surrounding medium. This was also observed after treating podocytes with the metalloproteinase ADAM17 or after overexpression of the Sdc4 core protein. Increased concentrations of Sdc4 ectodomain were detected in urine of rats during acute puromycin aminonucleoside nephrosis. Locally generated Sdc4 may play a role in regulating TRPC6 channels, and may contribute to glomerular pathology.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1853, Issue 10, Part A, October 2015, Pages 2610-2620
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1853, Issue 10, Part A, October 2015, Pages 2610-2620
نویسندگان
Eun Young Kim, Hila Roshanravan, Stuart E. Dryer,