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Author Notes:

Correspondence to: Rashidul Haque, PhD, Department of Ophthalmology, Emory University School of Medicine, Room B5600, 1365B Clifton Road, NE, Atlanta, GA, 30322; Phone: (404) 778-5642; FAX: (404) 778-2231; email: rhaque@emory.edu

RH designed experiments, supervised, analyzed data; RH and PMI wrote the paper; RH, EYH, ANF, and JCH performed luciferase assays and qRT-PCRs; ANF, EYH, and JCH performed cell culture. All authors read and approved the final manuscript. We are grateful to Dr. Machelle Pardue, Atlanta VA Center for Visual and Neurocognitive Rehabilitation, for donating rat retinal samples for this investigation.

The authors thank Ashley Ngo, Samantha Gokhale, Curran S. Sidhu, and Moe Hein Aung for technical assistance.

The authors declare no conflict of interest with respect to the research reported herein.

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Research Funding:

This research was supported by an unrestricted departmental award from Research to Prevent Blindness (RPB), Inc., and NIH grants R01EY004864, and P30EY006360.

MicroRNA-152 represses VEGF and TGFβ1 expressions through post-transcriptional inhibition of (Pro)renin receptor in human retinal endothelial cells

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Journal Title:

Molecular Vision

Volume:

Volume 21

Publisher:

, Pages 224-235

Type of Work:

Article | Final Publisher PDF

Abstract:

Purpose: The (pro)renin receptor (PRR), a component of the renin-angiotensin system (RAS), plays an important role in the physiologic and pathophysiological regulation of blood pressure and fluid/electrolyte homeostasis. The RAS including the PRR has been identified in retinal endothelial cells and other ocular tissues. In this study, the potential involvement of miRNAs in the posttranscriptional regulation of PRR was investigated in human retinal endothelial cells (hRECs) under high glucose (HG) conditions. Methods: miRNA-152 (miR-152) was identified in silico as a potential regulator of PRR, and this was confirmed by quantitative real-time PCR (qRT-PCR) and PRR 3′-untranslated region (UTR) reporter assays. Using RNA interference, both AT1R and PRR were implicated in the HG-mediated induction of vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR-2), and transforming growth factor β1 (TGFβ1). Results: The downregulation of miR-152 was observed in hRECs and rat retinal tissues under HG conditions. In parallel, PRR (target of miR-152), VEGF, VEGFR-2, and TGFβ1 at mRNA levels were elevated. However, the transfection of hRECs with miR-152 mimics in HG conditions resulted in the suppression of the PRR expression, as well as reduced VEGF, VEGFR-2, and TGFβ1 production. This was reversed by transfecting cells with the antisense (antagomir) of miR-152, suggesting the glucose-induced upregulation of VEGF, VEGFR-2, and TGFβ1 is mediated through PRR, and this regulation is likely achieved through the HG-mediated modulation of miRNAs. Conclusions: We have demonstrated that miR-152 interacting with PRR regulates downstream VEGF, VRGFR-2, and TGFβ1 expressions in hRECs in HG conditions. These studies suggest miR-152 and PRR may play a role in the pathogenesis of diabetic retinopathy (DR).

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© 2015 Molecular Vision.

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