Identification of cross-species shared transcriptional networks of diabetic
nephropathy in human and mouse glomeruli.
Authors Hodgin JB, Nair V, Zhang H, Randolph A, Harris RC, Nelson RG, Weil EJ, Cavalcoli
JD, Patel JM, Brosius FC, Kretzler M
Submitted By Matthias Kretzler on 3/7/2013
Status Published
Journal Diabetes
Year 2013
Date Published 1/1/2013
Volume : Pages 62 : 299 - 308
PubMed Reference 23139354
Abstract Murine models are valuable instruments in defining the pathogenesis of diabetic
nephropathy (DN), but they only partially recapitulate disease manifestations of
human DN, limiting their utility. To define the molecular similarities and
differences between human and murine DN, we performed a cross-species comparison
of glomerular transcriptional networks. Glomerular gene expression was profiled
in patients with early type 2 DN and in three mouse models (streptozotocin
DBA/2, C57BLKS db/db, and eNOS-deficient C57BLKS db/db mice). Species-specific
transcriptional networks were generated and compared with a novel
network-matching algorithm. Three shared human-mouse cross-species glomerular
transcriptional networks containing 143 (Human-DBA STZ), 97 (Human-BKS db/db),
and 162 (Human-BKS eNOS(-/-) db/db) gene nodes were generated. Shared nodes
across all networks reflected established pathogenic mechanisms of diabetes
complications, such as elements of Janus kinase (JAK)/signal transducer and
activator of transcription (STAT) and vascular endothelial growth factor
receptor (VEGFR) signaling pathways. In addition, novel pathways not previously
associated with DN and cross-species gene nodes and pathways unique to each of
the human-mouse networks were discovered. The human-mouse shared glomerular
transcriptional networks will assist DN researchers in selecting mouse models
most relevant to the human disease process of interest. Moreover, they will
allow identification of new pathways shared between mice and humans.

Investigators with authorship
Frank BrosiusUniversity of Arizona
Raymond HarrisVanderbilt University
Jeffrey HodginUniversity of Michigan-Ann Arbor
Matthias KretzlerUniversity of Michigan