title: MicroRNA-146b-3p regulates retinal inflammation by suppressing adenosine deaminase-2 in diabetes.
abstract: Hyperglycemia- (HG-) Amadori-glycated albumin- (AGA-) induced activation of microglia and monocytes and their adherence to retinal vascular endothelial cells contribute to retinal inflammation leading to diabetic retinopathy (DR). There is a great need for early detection of DR before demonstrable tissue damages become irreversible. Extracellular adenosine, required for endogenous anti-inflammation, is regulated by the interplay of equilibrative nucleoside transporter with adenosine deaminase (ADA) and adenosine kinase. ADA, including ADA1 and ADA2, exists in all organisms. However, because ADA2 gene has not been identified in mouse genome, how diabetes alters adenosine-dependent anti-inflammation remains unclear. Studies of pig retinal microglia and human macrophages revealed a causal role of ADA2 in inflammation. Database search suggested miR-146b-3p recognition sites in the 3'-UTR of ADA2 mRNA. Coexpression of miR-146b-3p, but not miR-146-5p or nontargeting miRNA, with 3'-UTR of the ADA2 gene was necessary to suppress a linked reporter gene. In the vitreous of diabetic patients, decreased miR-146b-3p is associated with increased ADA2 activity. Ectopic expression of miR-146b-3p suppressed ADA2 expression, activity, and TNF-α release in the AGA-treated human macrophages. These results suggest a regulatory role of miR-146b-3p in diabetes related retinal inflammation by suppressing ADA2.
authors: Department of Orthopedics, Georgia Regents University, Augusta, GA, USA.
authors: Sadanand
authors: S
authors: Fulzele
authors: Department of Ophthalmology, Georgia Regents University, Augusta, GA 30912, USA.
authors: Ahmed
authors: A
authors: El-Sherbini
authors: Rabigh College of Science and Arts, King Abdulaziz University, Jeddah, Saudi Arabia.
authors: Saif
authors: S
authors: Ahmad
authors: Department of Orthopedics, Georgia Regents University, Augusta, GA, USA.
authors: Rajnikumar
authors: R
authors: Sangani
authors: Program in Clinical and Experimental Therapeutics, University of Georgia, Augusta, GA, USA.
authors: Suraporn
authors: S
authors: Matragoon
authors: Program in Clinical and Experimental Therapeutics, University of Georgia, Augusta, GA, USA.
authors: Azza
authors: 0000-0003-4386-1989
authors: A
authors: El-Remessy
authors: Department of Ophthalmology, Georgia Regents University, Augusta, GA 30912, USA.
authors: Reshmitha
authors: R
authors: Radhakrishnan
authors: Department of Ophthalmology, Georgia Regents University, Augusta, GA 30912, USA.
authors: Gregory I
authors: GI
authors: Liou
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis* / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism; D000368:Aged; D000818:Animals; D001344:Autopsy; D004268:DNA-Binding Proteins; D003930:Diabetic Retinopathy / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis* / Q000378:metabolism; D008875:Middle Aged; D012160:Retina / Q000201:enzymology / Q000473:pathology; D013552:Swine; D014157:Transcription Factors / Q000096:biosynthesis* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; C097695:TADA2A protein, human; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D000241:Adenosine