کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10815790 | 1058503 | 2010 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Mathematical modelling of interferon-γ signalling in pancreatic stellate cells reflects and predicts the dynamics of STAT1 pathway activity
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کلمات کلیدی
Phosphorylated STAT1ECMA.U.SOCSIMDMPSCERKIRFHprtODEPVDFSDSIIRPBSJanus kinase - کیناز جانوس BSA - BSAIscove's modified Dulbecco's medium - Medculus Dulbecco اصلاح شده Iscove استStat1 - sTAT1bovine serum albumine - آلبومین سرم گاوSTAT - آمارinterferon - اینترفرونIFN - اینترفرون هاinterferon-γ - اینترفرون-γstandard error of the mean - خطای استاندارد میانگینRoom temperature - دمای اتاقsodium dodecyl sulphate - سدیم دودسیل سولفاتsuppressor of cytokine signalling - سرکوب کننده سیگنالینگ سیتوکینpancreatic stellate cell - سلول ستون لوزالمعدهPancreatic Stellate Cells - سلول های ستون فقرات پانکراسinterferon regulatory factor - عامل تنظیمی اینترفرونPhosphate buffered saline - فسفات بافر شورExtracellular matrix - ماتریکس خارج سلولیSignal transducer and activator of transcription - مبدل سیگنال و فعال کننده رونویسیMathematical modelling - مدل سازی ریاضیSEM - مدل معادلات ساختاری / میکروسکوپ الکترونی روبشیOrdinary differential equations - معادلهٔ دیفرانسیل معمولیhypoxanthine-guanine phosphoribosyl transferase - هیپوکسانتین-گوانین فسفریبوسیل ترانسفرازArbitrary Unit - واحد خودآموزJAK - چگونهextracellular regulated kinase - کیناز تنظیم شده خارج سلولی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Signal transducer and activator of transcription (STAT) 1 is essentially involved in the mediation of antifibrotic interferon-γ (IFNγ) effects in pancreatic stellate cells (PSC). Here, we have further analysed the activation of the STAT1 pathway in a PSC line by combining quantitative data generation with mathematical modelling. At saturating concentrations of IFNγ, a triphasic pattern of STAT1 activation was observed. An initial, rapid induction of phospho-STAT1 was followed by a plateau phase and another, long-lasting phase of further increase. The late increase occurred despite enhanced expression of the feedback inhibitor (SOCS1), and corresponded to increased levels of total STAT1 protein. If IFNγ was applied at non-saturating concentrations, phospho-STAT1 and SOCS1 levels peaked and declined again over a 12 hour period, while STAT1 protein levels remained high. The mathematical model, based on a system of ordinary differential equations, describes temporal changes of the network components as a function of interactions and transport processes. The model reproduced activation profiles of all components of the STAT1 pathway that were experimentally analysed. Furthermore, it successfully predicted the dynamics of network components in additional experimental studies. Based on experimental findings and the results obtained from modelling, we suggest exhaustion of applied IFNγ and STAT1 dephosphorylation by tyrosine phosphatases as limiting factors of STAT1 activation in PSC. In contrast, we did not obtain compelling evidence that SOCS1 acts as an efficient feedback inhibitor in our experimental system. We believe that further investigations into mathematical modelling of the STAT1 pathway will improve the understanding of the antifibrotic interferon action.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 22, Issue 1, January 2010, Pages 97-105
Journal: Cellular Signalling - Volume 22, Issue 1, January 2010, Pages 97-105
نویسندگان
Katja Rateitschak, Anna Karger, Brit Fitzner, Falko Lange, Olaf Wolkenhauer, Robert Jaster,