@article{328973b0bf974d30bfbb1747e628934a,
title = "Conserved Transcriptional Signatures in Human and Murine Diabetic Peripheral Neuropathy",
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.",
author = "McGregor, {Brett A.} and Stephanie Eid and Rumora, {Amy E.} and Benjamin Murdock and Kai Guo and {de Anda-J{\'a}uregui}, Guillermo and Porter, {James E.} and Feldman, {Eva L.} and Junguk Hur",
note = "Funding Information: B.A.M. performed bioinformatics analyses and wrote the manuscript. S.E., A.E.R. and B.M. wrote the manuscript. K.G. and G.A.J. performed bioinformatics analyses. J.P. contributed the discussion and revised the manuscript. E.L.F. and J.H. designed the study and wrote the manuscript. E.L.F. and J.H. are the guarantors of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. This work was supported by the U.S. National Institutes of Health (NIH 1 R24 DK082841 to E.L.F. and J.H.), the American Diabetes Association (to E.L.F.), the Novo Nordisk Foundation (to E.L.F.), the Program for Neurology Research and Discovery at University of Michigan, the A. Alfred Taubman Medical Research Institute, Juvenile Diabetes Research Foundation Postdoctoral Fellowships (to J.H.), the Applied Systems Biology Core of the George M. O{\textquoteright}Brien Michigan Kidney Translational Core Center (NIH P30 DK081943), the NIDDK Diabetic Complications Consortium Pilot Grant (DiaComp, www.diacomp.org; DK076169; Sub-award #25034-75) (to J.H.), and University of North Dakota Post-Doc Pilot Grant (to K.G.). Publisher Copyright: {\textcopyright} 2018, The Author(s).",
year = "2018",
month = dec,
day = "1",
doi = "10.1038/s41598-018-36098-5",
language = "English (US)",
volume = "8",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}