Transcriptional networks of progressive diabetic peripheral neuropathy in the
db/db mouse model of type 2 diabetes: An inflammatory story.
Authors Hinder LM, Murdock BJ, Park M, Bender DE, O'Brien PD, Rumora AE, Hur J, Feldman
Submitted By Junguk Hur on 11/5/2018
Status Published
Journal Experimental neurology
Year 2018
Date Published 7/1/2018
Volume : Pages 305 : 33 - 43
PubMed Reference 29550371
Abstract Diabetic peripheral neuropathy is the most common complication of diabetes and a
source of considerable morbidity. Numerous molecular pathways are linked to
neuropathic progression, but it is unclear whether these pathways are altered
throughout the course of disease. Moreover, the methods by which these molecular
pathways are analyzed can produce significantly different results; as such it is
often unclear whether previously published pathways are viable targets for novel
therapeutic approaches. In the current study we examine changes in gene
expression patterns in the sciatic nerve (SCN) and dorsal root ganglia (DRG) of
db/db diabetic mice at 8, 16, and 24?weeks of age using microarray analysis.
Following the collection and verification of gene expression data, we utilized
both self-organizing map (SOM) analysis and differentially expressed gene (DEG)
analysis to detect pathways that were altered at all time points. Though there
was some variability between SOM and DEG analyses, we consistently detected
altered immune pathways in both the SCN and DRG over the course of disease. To
support these results, we further used multiplex analysis to assess protein
changes in the SCN of diabetic mice; we found that multiple immune molecules
were upregulated at both early and later stages of disease. In particular, we
found that matrix metalloproteinase-12 was highly upregulated in microarray and
multiplex data sets suggesting it may play a role in disease progression.