کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8792094 | 1602556 | 2018 | 40 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
ANGPTL-4 induces diabetic retinal inflammation by activating Profilin-1
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
DOXProfilin-1Diabetic retinopathy (DR)PDRHuman retinal microvascular endothelial cellsT2DMHIF-1αSTZICAM-1GFAPAdipocytokine - آدیپوسیتوکینstreptozotocin - استرپتوزوتوسینSprague Dawley - اسپراگ داولیinflammation - التهاب( توروم) interleukin - اینترلوکینDoxorubicin - دوکسوروبیسینType 2 diabetes mellitus - دیابت نوع دوdiabetic retinopathy - رتینوپاتی دیابتیProliferative diabetic retinopathy - رتینوپاتی دیابتی پرولیفراتیوVascular endothelial growth factor - فاکتور رشد اندوتلیال عروقیVascular Endothelial Growth Factor (VEGF) - فاکتور رشد اندوتلیال عروقی (VEGF)hypoxia inducible factor-1 alpha - هیپوکسی القاء عامل 1 الفGlial fibrillary acidic protein - پروتئین اسیدی فیبریلاسیون گلایالhigh glucose - گلوکز بالا یا قند بالاnormal glucose - گلوکز طبیعی
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ایمونولوژی و میکروب شناسی (عمومی)
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Diabetic retinopathy (DR), the most common cause of irreversible blindness in working-age adults, results in central vision loss that is caused by microvascular damage to the inner lining of the back of the eye, the retina. The aim of this work was to assess the temporal relationships between angiopoietin-like protein-4 (ANGPTL-4), a novel adipocytokine factor, and diabetic retinal inflammation and microvascular dysfunction. The downstream pathway(s) and upstream mediator(s) of ANGPTL-4 were then determined under high glucose (HG) conditions. Diabetic rats and control animals were randomly assigned to receive hypoxia inducible factor-1 alpha (HIF-1α) blockade (doxorubicin or shRNA) or vehicle for 8 weeks. Human retinal microvascular endothelial cells (HRMECs) were incubated with normal or high glucose, with or without blockade or recombinant proteins, for ANGPTL-4, HIF-1α, and vascular endothelial growth factor (VEGF). The levels of ANGPTL-4, profilin-1, HIF-1α, VEGF, interleukin 1 beta (IL-1β), IL-6, and intercellular adherent molecule 1 (ICAM-1) in the rat retinas and HRMEC extracts were examined by Western blotting and real-time RT-PCR. The levels of ANGPTL-4, profilin-1, HIF-1α, and VEGF protein and mRNA were significantly higher in the diabetic rats and HG-exposed HRMECs. ANGPTL-4 was a potent modulator of increased inflammation, permeability, and angiogenesis via activation of the profilin-1 signaling pathway. Our results showed that ANGPTL-4 upregulation was induced by HG, which was dependent on HIF-1α activation that was also triggered by HG, both in vivo and in vitro. Our results suggest that targeting ANGPTL-4, alone or in combination with profilin-1, may be an effective therapeutic strategy and diagnostic screening biomarker for proliferative diabetic retinopathy and other vitreous-retinal inflammatory diseases.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Eye Research - Volume 166, January 2018, Pages 140-150
Journal: Experimental Eye Research - Volume 166, January 2018, Pages 140-150
نویسندگان
Qianyi Lu, Peirong Lu, Wei Chen, Li Lu, Zhi Zheng,