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

5 Citations (Scopus)

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

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Diabetic Neuropathies
Peripheral Nervous System Diseases
Genes
Systems Biology
Gene Regulatory Networks
Adipogenesis
Glucocorticoid Receptors
Diabetes Complications
Streptozocin
Peripheral Nerves
Chemokines
Cytokines

ASJC Scopus subject areas

  • General

Cite this

McGregor, B. A., Eid, S., Rumora, A. E., Murdock, B., Guo, K., de Anda-Jáuregui, G., ... 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

Conserved Transcriptional Signatures in Human and Murine Diabetic Peripheral Neuropathy. / McGregor, Brett A.; Eid, Stephanie; Rumora, Amy E.; Murdock, Benjamin; Guo, Kai; de Anda-Jáuregui, Guillermo; Porter, James E.; Feldman, Eva L.; Hur, Junguk.

In: Scientific Reports, Vol. 8, No. 1, 17678, 01.12.2018.

Research output: Contribution to journalArticle

McGregor, BA, Eid, S, Rumora, AE, Murdock, B, Guo, K, de Anda-Jáuregui, G, Porter, JE, Feldman, EL & Hur, J 2018, 'Conserved Transcriptional Signatures in Human and Murine Diabetic Peripheral Neuropathy', Scientific Reports, vol. 8, no. 1, 17678. https://doi.org/10.1038/s41598-018-36098-5
McGregor BA, Eid S, Rumora AE, Murdock B, Guo K, de Anda-Jáuregui G et al. Conserved Transcriptional Signatures in Human and Murine Diabetic Peripheral Neuropathy. Scientific Reports. 2018 Dec 1;8(1). 17678. https://doi.org/10.1038/s41598-018-36098-5
McGregor, Brett A. ; Eid, Stephanie ; Rumora, Amy E. ; Murdock, Benjamin ; Guo, Kai ; de Anda-Jáuregui, Guillermo ; Porter, James E. ; Feldman, Eva L. ; Hur, Junguk. / Conserved Transcriptional Signatures in Human and Murine Diabetic Peripheral Neuropathy. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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