کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10815459 | 1058475 | 2013 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Induction of renal fibrotic genes by TGF-β1 requires EGFR activation, p53 and reactive oxygen species
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
ECMactivin-like kinaseheparin-binding EGFHB-EGFMEFsERKCTGFDABCDKDPIEGFRα-SMAEGF3,3′-diaminobenzidine - 3،3'-diaminobenzidineALK - آلکα-smooth muscle actin - اکتین عضله آلفا صافIHC - ایمونوهیستوشیمیImmunohistochemistry - ایمونوهیستوشیمیchronic kidney disease - بیماری مزمن کلیویdiphenyleneiodonium chloride - دی فینیلنیدونیم کلریدepidermal growth factor - عامل رشد اپیدرمیConnective tissue growth factor - فاکتور رشد بافت همبندExtracellular matrix - ماتریکس خارج سلولیBMP - مدیریت فرایند کسب و کارbone morphogenic protein - پروتئین مورفولوژیک استخوانextracellular signal-regulated kinases - کیناز های تنظیم شده سیگنال خارج سلولیEpidermal growth factor receptor - گیرنده فاکتور رشد اپیدرمال
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
While transforming growth factor-β (TGF-β1)-induced SMAD2/3 signaling is a critical event in the progression of chronic kidney disease, the role of non-SMAD mechanisms in the orchestration of fibrotic gene changes remains largely unexplored. TGF-β1/SMAD3 pathway activation in renal fibrosis (induced by ureteral ligation) correlated with epidermal growth factor receptorY845 (EGFRY845) and p53Ser15 phosphorylation and induction of disease causative target genes plasminogen activator inhibitor-1 (PAI-1) and connective tissue growth factor (CTGF) prompting an investigation of the mechanistic involvement of EGFR and tumor suppressor p53 in profibrotic signaling. TGF-β1, PAI-1, CTGF, p53 and EGFR were co-expressed in the obstructed kidney localizing predominantly to the tubular and interstitial compartments. Indeed, TGF-β1 activated EGFR and p53 as well as SMAD2/3. Genetic deficiency of either EGFR or p53 or functional blockade with AG1478 or Pifithrin-α, respectively, effectively inhibited PAI-1and CTGF induction and morphological transformation of renal fibroblasts as did SMAD3 knockdown or pretreatment with the SMAD3 inhibitor SIS3. Reactive oxygen species (ROS)-dependent mechanisms initiated by TGF-β1 were critical for EGFRY845 and p53Ser15 phosphorylation and target gene expression. The p22Phox subunit of NADPH oxidase was also elevated in the fibrotic kidney with an expression pattern similar to p53 and EGFR. EGF stimulation alone initiated, albeit delayed, c-terminal SMAD3 phosphorylation (that required the TGF-β1 receptor) and rapid ERK2 activation both of which are necessary for PAI-1 and CTGF induction in renal fibroblasts. These data highlight the extensive cross-talk among SMAD2/3, EGFR and p53 pathways essential for expression of TGF-β1-induced fibrotic target genes.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 25, Issue 11, November 2013, Pages 2198-2209
Journal: Cellular Signalling - Volume 25, Issue 11, November 2013, Pages 2198-2209
نویسندگان
Rohan Samarakoon, Amy D. Dobberfuhl, Catherine Cooley, Jessica M. Overstreet, Samik Patel, Roel Goldschmeding, Kirstan K. Meldrum, Paul J. Higgins,