Conserved Transcriptional Signatures in Human and Murine Diabetic Peripheral
Authors McGregor BA, Eid S, Rumora AE, Murdock B, Guo K, de Anda-Jáuregui G, Porter JE,
Feldman EL, Hur J
Submitted By Junguk Hur on 2/5/2019
Status Published
Journal Scientific reports
Year 2018
Date Published 12/1/2018
Volume : Pages 8 : 17678
PubMed Reference 30518872
Abstract Diabetic peripheral neuropathy (DPN) is one of the most common complications of
diabetes. In this study, we employed a systems biology approach to identify
DPN-related transcriptional pathways conserved across human and various murine
models. Eight microarray datasets on peripheral nerve samples from murine models
of type 1 (streptozotocin-treated) and type 2 (db/db and ob/ob) diabetes of
various ages and human subjects with non-progressive and progressive DPN were
collected. Differentially expressed genes (DEGs) were identified between
non-diabetic and diabetic samples in murine models, and non-progressive and
progressive human samples using a unified analysis pipeline. A transcriptional
network for each DEG set was constructed based on literature-derived gene-gene
interaction information. Seven pairwise human-vs-murine comparisons using a
network-comparison program resulted in shared sub-networks including 46 to 396
genes, which were further merged into a single network of 688 genes. Pathway and
centrality analyses revealed highly connected genes and pathways including
LXR/RXR activation, adipogenesis, glucocorticoid receptor signalling, and
multiple cytokine and chemokine pathways. Our systems biology approach
identified highly conserved pathways across human and murine models that are
likely to play a role in DPN pathogenesis and provide new possible
mechanism-based targets for DPN therapy.