Dual Anti-Inflammatory and Anti-Angiogenic Action of miR-15a in Diabetic Retinopathy
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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2016-09-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396416303620 |
| _version_ | 1819148165770641408 |
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| author | Qi Wang Svetlana Navitskaya Harshini Chakravarthy Chao Huang Nermin Kady Todd A. Lydic Y. Eugene Chen Ke-Jie Yin Folami Lamoke Powell Pamela M. Martin Maria B. Grant Julia V. Busik |
| author_facet | Qi Wang Svetlana Navitskaya Harshini Chakravarthy Chao Huang Nermin Kady Todd A. Lydic Y. Eugene Chen Ke-Jie Yin Folami Lamoke Powell Pamela M. Martin Maria B. Grant Julia V. Busik |
| author_sort | Qi Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T13:41:23Z |
| format | Article |
| id | doaj.art-2a68a1d0185d4c5281617ed0199833fd |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-22T13:41:23Z |
| publishDate | 2016-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-2a68a1d0185d4c5281617ed0199833fd2022-12-21T18:23:55ZengElsevierEBioMedicine2352-39642016-09-0111C13815010.1016/j.ebiom.2016.08.013Dual Anti-Inflammatory and Anti-Angiogenic Action of miR-15a in Diabetic RetinopathyQi Wang0Svetlana Navitskaya1Harshini Chakravarthy2Chao Huang3Nermin Kady4Todd A. Lydic5Y. Eugene Chen6Ke-Jie Yin7Folami Lamoke Powell8Pamela M. Martin9Maria B. Grant10Julia V. Busik11Department of Physiology, Michigan State University, East Lansing, MI 48824, United StatesDepartment of Physiology, Michigan State University, East Lansing, MI 48824, United StatesDepartment of Physiology, Michigan State University, East Lansing, MI 48824, United StatesDepartment of Physiology, Michigan State University, East Lansing, MI 48824, United StatesDepartment of Physiology, Michigan State University, East Lansing, MI 48824, United StatesDepartment of Physiology, Michigan State University, East Lansing, MI 48824, United StatesDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, United StatesDepartment of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, United StatesThe Medical College of Georgia, at Augusta University, Augusta, GA 30912, United StatesThe Medical College of Georgia, at Augusta University, Augusta, GA 30912, United StatesDepartment of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN 46202, United StatesDepartment of Physiology, Michigan State University, East Lansing, MI 48824, United StatesActivation 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.http://www.sciencedirect.com/science/article/pii/S2352396416303620Diabetic retinopathymicroRNASphingolipidsDyslipidemiasVascular system injuries |
| spellingShingle | Qi Wang Svetlana Navitskaya Harshini Chakravarthy Chao Huang Nermin Kady Todd A. Lydic Y. Eugene Chen Ke-Jie Yin Folami Lamoke Powell Pamela M. Martin Maria B. Grant Julia V. Busik Dual Anti-Inflammatory and Anti-Angiogenic Action of miR-15a in Diabetic Retinopathy EBioMedicine Diabetic retinopathy microRNA Sphingolipids Dyslipidemias Vascular system injuries |
| title | Dual Anti-Inflammatory and Anti-Angiogenic Action of miR-15a in Diabetic Retinopathy |
| title_full | Dual Anti-Inflammatory and Anti-Angiogenic Action of miR-15a in Diabetic Retinopathy |
| title_fullStr | Dual Anti-Inflammatory and Anti-Angiogenic Action of miR-15a in Diabetic Retinopathy |
| title_full_unstemmed | Dual Anti-Inflammatory and Anti-Angiogenic Action of miR-15a in Diabetic Retinopathy |
| title_short | Dual Anti-Inflammatory and Anti-Angiogenic Action of miR-15a in Diabetic Retinopathy |
| title_sort | dual anti inflammatory and anti angiogenic action of mir 15a in diabetic retinopathy |
| topic | Diabetic retinopathy microRNA Sphingolipids Dyslipidemias Vascular system injuries |
| url | http://www.sciencedirect.com/science/article/pii/S2352396416303620 |
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