کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8298449 | 1536895 | 2018 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Involvement of the ubiquitin-proteasome system in the expression of extracellular matrix genes in retinal pigment epithelial cells
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
ECMARPE-19CNVnAMDCTGFAMDMMP-2PPARγIFNγChoroidal neovascularization - neovascularization choroidalinterferon-γ - اینترفرون-γEMT - تکنسین فوریتهای پزشکیneovascular age-related macular degeneration - دژنراسیون ماکولار مرتبط با سن انقباض عضلانیHuman retinal pigment epithelial cells - سلول های اپیتلیال رنگدانه شبکیه انسانage-related macular degeneration - سن تخریب ماکولا مربوط به سن استConnective tissue growth factor - فاکتور رشد بافت همبندFibronectin - فیبرونکتینExtracellular matrix - ماتریکس خارج سلولیMatrix metalloproteinase-2 - ماتریکس متالوپروتئیناز-2Epithelial-mesenchymal transition - گذار اپیتلیال-مزانشیمی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Emerging evidence suggests that dysfunction of the ubiquitin-proteasome system is involved in the pathogenesis of numerous senile degenerative diseases including retinal disorders. The aim of this study was to assess whether there is a link between proteasome regulation and retinal pigment epithelium (RPE)-mediated expression of extracellular matrix genes. For this purpose, human retinal pigment epithelial cells (ARPE-19) were treated with different concentrations of transforming growth factor-β (TGFβ), connective tissue growth factor (CTGF), interferon-γ (IFNγ) and the irreversible proteasome inhibitor epoxomicin. First, cytotoxicity and proliferation assays were carried out. The expression of proteasome-related genes and proteins was assessed and proteasome activity was determined. Then, expression of fibrosis-associated factors fibronectin (FN), fibronectin EDA domain (FN EDA), metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinases-1 (TIMP-1) and peroxisome proliferator-associated receptor-γ (PPARγ) was assessed. The proteasome inhibitor epoxomicin strongly arrested cell cycle progression and down-regulated TGFβ gene expression, which in turn was shown to induce expression of pro-fibrogenic genes in ARPE-19 cells. Furthermore, epoxomicin induced a directional shift in the balance between MMP-2 and TIMP-1 and was associated with down-regulation of transcription of extracellular matrix genes FN and FN-EDA and up-regulation of the anti-fibrogenic factor PPARγ. In addition, both CTGF and TGFβ were shown to affect expression of proteasome-associated mRNA and protein levels. Our results suggest a link between proteasome activity and pro-fibrogenic mechanisms in the RPE, which could imply a role for proteasome-modulating agents in the treatment of retinal disorders characterized by RPE-mediated fibrogenic responses.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemistry and Biophysics Reports - Volume 13, March 2018, Pages 83-92
Journal: Biochemistry and Biophysics Reports - Volume 13, March 2018, Pages 83-92
نویسندگان
J. Emanuel Ramos de Carvalho, Milan T. Verwoert, Ilse M.C. Vogels, Eric A. Reits, Cornelis J.F. Van Noorden, Ingeborg Klaassen, Reinier O. Schlingemann,