@article{c686679709f5437a89281e92910a97ab,
title = "Dual Anti-Inflammatory and Anti-Angiogenic Action of miR-15a in Diabetic Retinopathy",
abstract = "Activation of pro-inflammatory and pro-angiogenic pathways in the retina and the bone marrow contributes to pathogenesis of diabetic retinopathy. We identified miR-15a as key regulator of both pro-inflammatory and pro-angiogenic pathways through direct binding and inhibition of the central enzyme in the sphingolipid metabolism, ASM, and the pro-angiogenic growth factor, VEGF-A. miR-15a was downregulated in diabetic retina and bone marrow cells. Over-expression of miR-15a downregulated, and inhibition of miR-15a upregulated ASM and VEGF-A expression in retinal cells. In addition to retinal effects, migration and retinal vascular repair function was impaired in miR-15a inhibitor-treated circulating angiogenic cells (CAC). Diabetic mice overexpressing miR-15a under Tie-2 promoter had normalized retinal permeability compared to wild type littermates. Importantly, miR-15a overexpression led to modulation toward nondiabetic levels, rather than complete inhibition of ASM and VEGF-A providing therapeutic effect without detrimental consequences of ASM and VEGF-A deficiencies.",
keywords = "Diabetic retinopathy, Dyslipidemias, Sphingolipids, Vascular system injuries, microRNA",
author = "Qi Wang and Svetlana Navitskaya and Harshini Chakravarthy and Chao Huang and Nermin Kady and Lydic, {Todd A.} and Chen, {Y. Eugene} and Yin, {Ke Jie} and Powell, {Folami Lamoke} and Martin, {Pamela M.} and Grant, {Maria B.} and Busik, {Julia V.}",
note = "Funding Information: We thank Juvenile Diabetes Research Foundation (JDRF) Fellowship JDRF 3-PDF-2014-108-A-N to Q.W, National Institutes of Health (NIH) grant EY-01-6077, Michigan AgBioResearch grant MICL02163 to JVB, NIH grants EY-07739 and EY-12601 to MBG, Jean P Schultz Research Award to JVB, and NIH grant DK-09-0730 to MBG and JVB. Mass spectrometry analysis was provided by the Molecular Metabolism and Disease Collaborative Mass Spectrometry Core at Michigan State University. JVB is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. All of funding sources had no role in study design, data collection, data analysis, interpretation, writing of the manuscript or the decision to submit it for publication. I have not been paid to write this article by a pharmaceutical company or other agency. Publisher Copyright: {\textcopyright} 2016 Forschungsgesellschaft f{\"u}r Arbeitsphysiologie und Arbeitschutz e.V.",
year = "2016",
month = sep,
day = "1",
doi = "10.1016/j.ebiom.2016.08.013",
language = "English (US)",
volume = "11",
pages = "138--150",
journal = "EBioMedicine",
issn = "2352-3964",
publisher = "Elsevier BV",
}
