کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6002574 | 1182972 | 2012 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Assembly of the prothrombinase complex on the surface of human foreskin fibroblasts: Implications for connective tissue growth factor
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کلمات کلیدی
LAPTGFβRITSP1CTGF/CCN2latent TGFβ binding proteinTFPIFXaFVIIHFFLTBPHBSSTGFβDMEMqPCRPVDFcDNA - cDNAComplementary DNA - DNA تکمیلیDulbecco's modified Eagle Medium - Eagle Medium اصلاح شده DulbeccoSDS-PAGE - الکتروفورز ژل پلی آکریل آمیدTransforming Growth Factor Beta - تبدیل بتا فاکتور رشدanalysis of variances - تجزیه و تحلیل واریانسANOVA - تحلیل واریانس Analysis of varianceThrombospondin-1 - ترومبوسپوندن-1Thrombin - ترومبین یا فاکتور II Par - توسطTissue factor - عامل بافتFactor V - فاکتور VFactor VII - فاکتور VIIFactor X - فاکتور XConnective tissue growth factor - فاکتور رشد بافت همبندactivated Factor X - فعال عامل XFibroblasts - فیبروبلاست هاhuman foreskin fibroblasts - فیبروبلاستهای مزرعه انسانی انسانTissue factor pathway inhibitor - مهار کننده پروتئین بافتیreal-time polymerase chain reaction - واکنش زنجیره ای پلیمراز واقعی در زمان واقعیprothrombin - پروترومبینPolyvinylidene fluoride - پلی وینیلیدین فلوراید
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Activated factor X (FXa) and thrombin can up-regulate gene expression of connective tissue growth factor (CTGF/CCN2) on fibroblasts. Since tissue factor (TF) is expressed on these cells, we hypothesized that they may assemble the prothrombinase complex leading to CTGF/CCN2 upregulation. In addition, the effect of thrombospondin-1 (TSP1) on this reaction was evaluated. Human foreskin fibroblasts were incubated with purified factor VII (FVII), factor X (FX), factor V (FV), prothrombin and calcium in the presence and absence of TSP1. Generation of FXa and of thrombin were assessed using chromogenic substrates. SMAD pathway phosphorylation was detected via Western-blot analysis. Pre-incubation of fibroblasts with FVII led to its auto-activation by cell-surface expressed TF, which in turn in the presence of FX, FVa, prothrombin and calcium led to FXa (9.7 ± 0.8 nM) and thrombin (7.9 ± 0.04 U/mL Ã 10-3) generation. Addition of TSP1 significantly enhanced thrombin (23.3 ± 0.7 U/mL Ã 10-3) but not FXa (8.5 ± 0.6 nM) generation. FXa and thrombin generation leads to upregulation of CTGF/CCN2. TSP1 alone upregulated CTGF/CCN2, an effect mediated via activation of transforming growth factor beta (TGFβ) as shown by phosphorylation of the SMAD pathway, an event blunted by using a TGFβ receptor I inhibitor (TGFβRI). FXa- and thrombin-induced upregulation of CTGF/CCN2 was not blocked by TGFβRI. In summary, assembly of the prothrombinase complex occurs on fibroblast's surface leading to serine proteases generation, an event enhanced by TSP1 and associated with CTGF/CCN2 upregulation. These mechanisms may play an important role in human diseases associated with fibrosis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Thrombosis Research - Volume 129, Issue 6, June 2012, Pages 801-806
Journal: Thrombosis Research - Volume 129, Issue 6, June 2012, Pages 801-806
نویسندگان
Mario C. Rico, James J. Rough, Joanne M. Manns, Fabiola Del Carpio-Cano, Fayez F. Safadi, Satya P. Kunapuli, Raul A. DeLa Cadena,