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IMPC / KOMP Data
Conserved Transcriptional Signatures in Human and Murine Diabetic Peripheral
McGregor BA, Eid S, Rumora AE, Murdock B, Guo K, de Anda-Jáuregui G, Porter JE,
Feldman EL, Hur J
Junguk Hur on 2/5/2019
Volume : Pages
8 : 17678
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.
Neuropathy & Neurocognition
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All rights reserved
Please acknowledge all posters, manuscripts or scientific materials that were generated in part or whole using funds from the Diabetic Complications Consortium(DiaComp) using the following text:
Financial support for this work provided by the NIDDK Diabetic Complications Consortium (RRID:SCR_001415, www.diacomp.org), grants DK076169 and DK115255
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