MicroRNA-146b-3p regulates retinal inflammation by suppressing adenosine deaminase-2 in diabetes

Sadanand T Fulzele, Ahmed El-Sherbini, Saif Ahmad, Rajnikumar Sangani, Suraporn Matragoon, Azza El-Remessy, Reshmitha Radhakrishnan, Gregory I Liou

Research output: Contribution to journalArticle

34 Citations (Scopus)

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.

Original languageEnglish (US)
Article number846501
JournalBioMed Research International
Volume2015
DOIs
StatePublished - Jan 1 2015

Fingerprint

Adenosine Deaminase
Medical problems
MicroRNAs
Genes
Inflammation
Macrophages
3' Untranslated Regions
Adenosine
Microglia
Diabetic Retinopathy
Nucleoside Transport Proteins
Adenosine Kinase
Endothelial cells
Retinal Vessels
Reporter Genes
Hyperglycemia
Chemical activation
Tissue
Monocytes
Swine

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Fulzele, S. T., El-Sherbini, A., Ahmad, S., Sangani, R., Matragoon, S., El-Remessy, A., ... Liou, G. I. (2015). MicroRNA-146b-3p regulates retinal inflammation by suppressing adenosine deaminase-2 in diabetes. BioMed Research International, 2015, [846501]. https://doi.org/10.1155/2015/846501

MicroRNA-146b-3p regulates retinal inflammation by suppressing adenosine deaminase-2 in diabetes. / Fulzele, Sadanand T; El-Sherbini, Ahmed; Ahmad, Saif; Sangani, Rajnikumar; Matragoon, Suraporn; El-Remessy, Azza; Radhakrishnan, Reshmitha; Liou, Gregory I.

In: BioMed Research International, Vol. 2015, 846501, 01.01.2015.

Research output: Contribution to journalArticle

Fulzele, ST, El-Sherbini, A, Ahmad, S, Sangani, R, Matragoon, S, El-Remessy, A, Radhakrishnan, R & Liou, GI 2015, 'MicroRNA-146b-3p regulates retinal inflammation by suppressing adenosine deaminase-2 in diabetes', BioMed Research International, vol. 2015, 846501. https://doi.org/10.1155/2015/846501
Fulzele, Sadanand T ; El-Sherbini, Ahmed ; Ahmad, Saif ; Sangani, Rajnikumar ; Matragoon, Suraporn ; El-Remessy, Azza ; Radhakrishnan, Reshmitha ; Liou, Gregory I. / MicroRNA-146b-3p regulates retinal inflammation by suppressing adenosine deaminase-2 in diabetes. In: BioMed Research International. 2015 ; Vol. 2015.
@article{2cdf3f48c13042069b7e93c53bfbdef0,
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.",
author = "Fulzele, {Sadanand T} and Ahmed El-Sherbini and Saif Ahmad and Rajnikumar Sangani and Suraporn Matragoon and Azza El-Remessy and Reshmitha Radhakrishnan and Liou, {Gregory I}",
year = "2015",
month = "1",
day = "1",
doi = "10.1155/2015/846501",
language = "English (US)",
volume = "2015",
journal = "BioMed Research International",
issn = "2314-6133",
publisher = "Hindawi Publishing Corporation",

}

TY - JOUR

T1 - MicroRNA-146b-3p regulates retinal inflammation by suppressing adenosine deaminase-2 in diabetes

AU - Fulzele, Sadanand T

AU - El-Sherbini, Ahmed

AU - Ahmad, Saif

AU - Sangani, Rajnikumar

AU - Matragoon, Suraporn

AU - El-Remessy, Azza

AU - Radhakrishnan, Reshmitha

AU - Liou, Gregory I

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84925308649&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84925308649&partnerID=8YFLogxK

U2 - 10.1155/2015/846501

DO - 10.1155/2015/846501

M3 - Article

VL - 2015

JO - BioMed Research International

JF - BioMed Research International

SN - 2314-6133

M1 - 846501

ER -