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MicroRNA-146a Mimics Reduce the Peripheral Neuropathy in Type 2 Diabetic Mice.
- Source :
- Diabetes; Dec2017, Vol. 66 Issue 12, p3111-3121, 11p, 2 Color Photographs, 1 Chart, 5 Graphs
- Publication Year :
- 2017
-
Abstract
- MicroRNA-146a (miR-146a) regulates multiple immune diseases. However, the role of miR-146a in diabetic peripheral neuropathy (DPN) has not been investigated. We found that mice (db/db) with type 2 diabetes exhibited substantial downregulation of miR-146a in sciatic nerve tissue. Systemic administration of miR-146a mimics to diabetic mice elevated miR-146a levels in plasma and sciatic nerve tissue and substantially increased motor and sensory nerve conduction velocities by 29 and 11%, respectively, and regional blood flow by 50% in sciatic nerve tissue. Treatment with miR-146a mimics also considerably decreased the response in db/db mice to thermal stimuli thresholds. Histopathological analysis showed that miR-146a mimics markedly augmented the density of fluorescein isothiocyanate-dextran-perfused blood vessels and increased the number of intraepidermal nerve fibers, myelin thickness, and axonal diameters of sciatic nerves. In addition, miR-146a treatment reduced and increased classically and alternatively activated macrophage phenotype markers, respectively. Analysis of miRNA target array revealed that miR-146a mimics greatly suppressed expression of many proinflammatory genes and downstream related cytokines. Collectively, our data indicate that treatment of diabetic mice with miR-146a mimics robustly reduces DPN and that suppression of hyperglycemia-induced proinflammatory genes by miR-146a mimics may underlie its therapeutic effect. [ABSTRACT FROM AUTHOR]
- Subjects :
- TREATMENT of peripheral neuropathy
TYPE 2 diabetes treatment
MICRORNA
DOWNREGULATION
LABORATORY mice
HYPERGLYCEMIA treatment
DIABETIC neuropathies
RNA physiology
NERVE tissue
TYPE 2 diabetes complications
ANIMAL experimentation
BLOOD circulation
CARRIER proteins
CYTOKINES
IMMUNITY
MICE
PROTEINS
RESEARCH funding
DNA-binding proteins
SCIATIC nerve
PHYSIOLOGY
PREVENTION
Subjects
Details
- Language :
- English
- ISSN :
- 00121797
- Volume :
- 66
- Issue :
- 12
- Database :
- Complementary Index
- Journal :
- Diabetes
- Publication Type :
- Academic Journal
- Accession number :
- 126343598
- Full Text :
- https://doi.org/10.2337/db16-1182