Transcriptional networks of progressive diabetic peripheral neuropathy in the db/db mouse model of type 2 diabetes: An inflammatory story

Lucy M. Hinder, Benjamin J. Murdock, Meeyoung Park, Diane E. Bender, Phillipe D. O'Brien, Amy E. Rumora, Junguk Hur, Eva L. Feldman

Research output: Contribution to journalArticle

9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)33-43
Number of pages11
JournalExperimental Neurology
Volume305
DOIs
StatePublished - Jul 2018

Keywords

  • Diabetes
  • Diabetic peripheral neuropathy
  • Gene expression analysis
  • Immune system
  • Inflammation
  • Microarray
  • Mouse models
  • Self-organizing map
  • db/db

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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