کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10816177 | 1058543 | 2013 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
MicroRNA-dependent cross-talk between VEGF and HIF1α in the diabetic retina
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کلمات کلیدی
mRNAHIF1αMREICAM-1DKK1messenger RNA - RNA messengerDiabetes mellitus - دیابت قندیdiabetic retinopathy - رتینوپاتی دیابتیCompeting endogenous RNA - رقابت RNA درونیceRNA - سینهhypoxia-inducible factor 1-alpha - عامل القایی هیپوکسی 1-آلفاintercellular adhesion molecule-1 - مولکول چسبندگی بین سلولی -1MicroRNA - میکرو RNA MiRNA - میکروRNA، ریزآرانای، miRNADickkopf-1 - نادان 1Pten - ژن PTENhigh glucose - گلوکز بالا یا قند بالاnormal glucose - گلوکز طبیعی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
Both HIF1α (hypoxia-inducible factor alpha) and VEGF (vascular endothelial growth factor) are implicated in the pathogenesis of diabetic retinopathy (DR). Competitive endogenous RNAs (ceRNAs) are messenger RNA (mRNA) molecules that affect each other expression through competition for their shared microRNAs (miRNA). However, little is known about the role of ceRNAs in DR. We assess whether the expression of HIF1α and VEGF in DR is interdependent through sequestration of common miRNAs. We used bioinformatics to identify potential miRNAs that affect both genes and validated the interdependence of the genes by silencing or overexpression of the genes and assessed the luciferase-HIF1α 3â²UTR activity. We found that HIF1α and VEGF are targeted by 12 common miRNAs. Silencing either HIF1α or VEGF increased the availabilities of the shared miRNAs, therefore suppressed the luciferase-HIF1α 3â²UTR activity, whereas over-expressing HIF1α or VEGF increased the luciferase activity. HIF1α was co-expressed with VEGF in-vivo and in-vitro in DR models. Silencing HIF1α transcripts resulted in a significant reduction in VEGF protein levels and vice versa. This interdependence was miRNA- and 3â²UTR-dependent, as silencing Dicer abolished the interdependence. Over-expression of a common miRNA (miR-106a) significantly reduced the expression of HIF1α and VEGF and prevented high glucose-induced increased permeability. There is a cross-talk between HIF1α and VEGF through interactions with their common miRNAs. miRNA based therapy can affect the expression of both HIF1α and VEGF and may represent a therapeutic potential for the treatment of DR.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 25, Issue 12, December 2013, Pages 2840-2847
Journal: Cellular Signalling - Volume 25, Issue 12, December 2013, Pages 2840-2847
نویسندگان
Shukuan Ling, Yochai Birnbaum, Manjyot K Nanhwan, Bejoy Thomas, Mandeep Bajaj, Yumei Ye,