کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8956038 | 1646123 | 2018 | 39 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Activation of renal profibrotic TGFβ controlled signaling cascades by calcineurin and mTOR inhibitors
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کلمات کلیدی
Latency-associated proteinLAPCNITβRECMAP-1ERKJun N-terminal kinaseTGFβFKBPmTORJnkTGFβ receptorMMPNF-κBMAPK - MAPKMAPK/ERK kinase - MAPK / ERK kinaseROS - ROSepithelial to mesenchymal transition - اپیتلیال به انتقال مزانشیمالTransforming growth factor β - تبدیل فاکتور رشد βEMT - تکنسین فوریتهای پزشکیSOD - سدmesangial cells - سلول های مزانژیSuperoxide dismutase - سوکسوکس دیسموتازextracellular signal regulated kinase - سیگنال خارج سلولی kinase را تنظیم می کندnuclear factor κB - فاکتور هسته ای κBFibrosis - فیبروز یا فساد الیافExtracellular matrix - ماتریکس خارج سلولیmatrix metalloproteinase - ماتریکس متالوپروتئینازMEK - مجاهدین خلقCalcineurin inhibitors - مهار کننده های کالسینورینmTOR inhibitors - مهارکننده های mTORMechanistic target of rapamycin - هدف مکانیکی رپامایسینFK506 binding protein - پروتئین اتصال FK506activator protein 1 - پروتئین فعال کننده 1mitogen activated protein kinase - پروتئین کیناز فعال Mitogen فعال استReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Activation of renal profibrotic TGFβ controlled signaling cascades by calcineurin and mTOR inhibitors Activation of renal profibrotic TGFβ controlled signaling cascades by calcineurin and mTOR inhibitors](/preview/png/8956038.png)
چکیده انگلیسی
The calcineurin inhibitors (CNI) cyclosporine A (CsA) and tacrolimus represent potent immunosuppressive agents frequently used for solid organ transplantation and treatment of autoimmune disorders. Despite of their immense therapeutic benefits, residual fibrosis mainly in the kidney represents a common side effect of long-term therapy with CNI. Regardless of the immunosuppressive action, an increasing body of evidence implicates that a drug-induced increase in TGFβ and subsequent activation of TGFβ-initiated signaling pathways is closely associated with the development and progression of CNI-induced nephropathy. Mechanistically, an increase in reactive oxygen species (ROS) generation due to drug-induced changes in the intracellular redox homeostasis functions as an important trigger of the profibrotic signaling cascades activated under therapy with CNI. Although, inhibitors of the mechanistic target of rapamycin (mTOR) kinase have firmly been established as alternative compounds with a lower nephrotoxic potential, an activation of fibrogenic signaling cascades has been reported for these drugs as well. This review will comprehensively summarize recent advances in the understanding of profibrotic signaling events modulated by these widely used compounds with a specific focus put on mechanisms occurring independent of their respective immunosuppressive action. Herein, the impact of redox modulation, the activation of canonical TGFβ and non-Smad pathways and modulation of autophagy by both classes of immunosuppressive drugs will be highlighted and discussed in a broader perspective. The comprehensive knowledge of profibrotic signaling events specifically accompanying the immunomodulatory activity of these widely used drugs is needed for a reliable benefit-risk assessment under therapeutic regimens.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 52, December 2018, Pages 1-11
Journal: Cellular Signalling - Volume 52, December 2018, Pages 1-11
نویسندگان
Wolfgang Eberhardt, Usman Nasrullah, Josef Pfeilschifter,