Conserved Transcriptional Signatures in Human and Murine Diabetic Peripheral Neuropathy

Brett A. McGregor, Stephanie Eid, Amy E. Rumora, Benjamin Murdock, Kai Guo, Guillermo de Anda-Jáuregui, James E. Porter, Eva L. Feldman, Junguk Hur

Research output: Contribution to journalArticle

13 Scopus citations

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.

Original languageEnglish (US)
Article number17678
JournalScientific reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

ASJC Scopus subject areas

  • General

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    McGregor, B. A., Eid, S., Rumora, A. E., Murdock, B., Guo, K., de Anda-Jáuregui, G., Porter, J. E., Feldman, E. L., & Hur, J. (2018). Conserved Transcriptional Signatures in Human and Murine Diabetic Peripheral Neuropathy. Scientific reports, 8(1), [17678]. https://doi.org/10.1038/s41598-018-36098-5