Please use this identifier to cite or link to this item: doi:10.22028/D291-30513
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Title: Identification of novel diabetes impaired miRNA-transcription factor co-regulatory networks in bone marrow-derived Lin-/VEGF-R2+ endothelial progenitor cells
Author(s): Irhimeh, Mohammad R.
Hamed, Mohamed
Barthelmes, Daniel
Gladbach, Yvonne
Helms, Volkhard
Shen, Weiyong
Gillies, Mark C.
Language: English
Volume: 13
Issue: 7
Startpage: 1
Endpage: 20
Publisher/Platform: PLOS
Year of Publication: 2018
Publikation type: Journal Article
Abstract: Endothelial progenitor cells (EPCs) are a group of rare cells that play an important role in the repair of injured vascular endothelial cells and assist in reperfusion of ischemic tissue. Decreased production and/or loss of function of EPCs are associated with diabetic vasculopathy. The molecular mechanisms by which diabetes impairs EPCs remain unclear. We conducted microarray experiments followed by integrative regulatory analysis on cells isolated from Akita diabetic mice (18-weeks after onset of diabetes) and age-matched non-diabetic controls. Two types of cells were isolated from mice bone marrow; Lin+ cells and Lin-/VEGF-R2+ EPCs. RNA was hybridized to mouse WG-6 V2 beadchips followed by comprehensive gene network analysis and computational validation of the obtained results. In total, 80 genes were exclusively DE between non-diabetic Lin-/VEGF-R2+ EPCs and diabetic Lin-/VEGF-R2+ EPCs, of which the 3 genes Clcnka, Pik3c2a, and Ptf1a are known to be associated with diabetic complications. Further analysis led to the establishment of a TF-miRNA mediated regulatory network specific to diabetic Lin-/VEGF-R2+ EPCs and to identify 11 central-hub TFs (Tbp, Ahr, Trp53, Gata1, Foxo1, Foxo4, Yy1, Max, Pparg, Myc, Cebpa), and 2 miRNAs (mir-139-5p, mir-709) that might act as putative genomic drivers of diabetic pathogenesis in Lin-/VEGF-R2+ EPCs. Moreover, we identified multiple TF-miRNA co-regulatory network motifs for which we validated their contribution to diabetic Lin-/VEGF-R2+ EPCs in terms of statistical significance and relevance to biological evidence. Our findings suggest that diabetic Lin-/VEGF-R2+ EPCs have specifically altered signature genes and miRNAs that render their capacity to proliferate and differentiate.
DOI of the first publication: 10.1371/journal.pone.0200194
URL of the first publication:
Link to this record: hdl:20.500.11880/28890
ISSN: 1932-6203
Date of registration: 20-Mar-2020
Faculty: NT - Naturwissenschaftlich- Technische Fakultät
Department: NT - Biowissenschaften
Professorship: NT - Prof. Dr. Volkhard Helms
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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