Dual Anti-Inflammatory and Anti-Angiogenic Action of miR-15a in Diabetic Retinopathy

Qi Wang, Svetlana Navitskaya, Harshini Chakravarthy, Chao Huang, Nermin Kady, Todd A. Lydic, Y. Eugene Chen, Ke Jie Yin, Folami Lamoke Powell, Pamela Moore Martin, Maria B. Grant, Julia V. Busik

Research output: Contribution to journalArticle

29 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)138-150
Number of pages13
JournalEBioMedicine
Volume11
DOIs
StatePublished - Sep 1 2016

Fingerprint

Diabetic Retinopathy
Vascular Endothelial Growth Factor A
Anti-Inflammatory Agents
Retina
Bone
Down-Regulation
Cells
Enzyme inhibition
Retinal Vessels
Sphingolipids
Angiogenesis Inducing Agents
Therapeutic Uses
Metabolism
Bone Marrow Cells
Permeability
Intercellular Signaling Peptides and Proteins
Repair
Bone Marrow
Chemical activation
Modulation

Keywords

  • Diabetic retinopathy
  • Dyslipidemias
  • Sphingolipids
  • Vascular system injuries
  • microRNA

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Wang, Q., Navitskaya, S., Chakravarthy, H., Huang, C., Kady, N., Lydic, T. A., ... Busik, J. V. (2016). Dual Anti-Inflammatory and Anti-Angiogenic Action of miR-15a in Diabetic Retinopathy. EBioMedicine, 11, 138-150. https://doi.org/10.1016/j.ebiom.2016.08.013

Dual Anti-Inflammatory and Anti-Angiogenic Action of miR-15a in Diabetic Retinopathy. / Wang, Qi; Navitskaya, Svetlana; Chakravarthy, Harshini; Huang, Chao; Kady, Nermin; Lydic, Todd A.; Chen, Y. Eugene; Yin, Ke Jie; Powell, Folami Lamoke; Martin, Pamela Moore; Grant, Maria B.; Busik, Julia V.

In: EBioMedicine, Vol. 11, 01.09.2016, p. 138-150.

Research output: Contribution to journalArticle

Wang, Q, Navitskaya, S, Chakravarthy, H, Huang, C, Kady, N, Lydic, TA, Chen, YE, Yin, KJ, Powell, FL, Martin, PM, Grant, MB & Busik, JV 2016, 'Dual Anti-Inflammatory and Anti-Angiogenic Action of miR-15a in Diabetic Retinopathy', EBioMedicine, vol. 11, pp. 138-150. https://doi.org/10.1016/j.ebiom.2016.08.013
Wang Q, Navitskaya S, Chakravarthy H, Huang C, Kady N, Lydic TA et al. Dual Anti-Inflammatory and Anti-Angiogenic Action of miR-15a in Diabetic Retinopathy. EBioMedicine. 2016 Sep 1;11:138-150. https://doi.org/10.1016/j.ebiom.2016.08.013
Wang, Qi ; Navitskaya, Svetlana ; Chakravarthy, Harshini ; Huang, Chao ; Kady, Nermin ; Lydic, Todd A. ; Chen, Y. Eugene ; Yin, Ke Jie ; Powell, Folami Lamoke ; Martin, Pamela Moore ; Grant, Maria B. ; Busik, Julia V. / Dual Anti-Inflammatory and Anti-Angiogenic Action of miR-15a in Diabetic Retinopathy. In: EBioMedicine. 2016 ; Vol. 11. pp. 138-150.
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