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Open Access Original investigation

Differential gene expression in Lin-/VEGF-R2+ bone marrow-derived endothelial progenitor cells isolated from diabetic mice

Daniel Barthelmes, Ling Zhu, Weiyong Shen, Mark C Gillies and Mohammad R Irhimeh*

Author Affiliations

Save Sight Institute, Level 1, South Block Sydney Hospital and Sydney Eye Hospital, Central Clinical School, The University of Sydney, 8 Macquarie Street, Sydney, NSW 2000, Australia

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Cardiovascular Diabetology 2014, 13:42  doi:10.1186/1475-2840-13-42

Published: 12 February 2014

Abstract

Background

Diabetes is known to impair the number and function of endothelial progenitor cells in the circulation, causing structural and functional alterations in the micro- and macro-vasculature. The aim of this study was to identify early diabetes-related changes in the expression of genes that have been reported to be closely involved in endothelial progenitor cell migration and function.

Methods

Based on review of current literature, this study examined the expression level of 35 genes that are known to be involved in endothelial progenitor cell migration and function in magnetically sorted Lin-/VEGF-R2+ endothelial progenitor cells obtained from the bone marrow of Akita mice in the early stages of diabetes (18 weeks) using RT-PCR and Western blotting. We used the Shapiro-Wilk and D’Agostino & Pearson Omnibus tests to assess normality. Differences between groups were evaluated by Student’s t-test for normally distributed data (including Welch correction in cases of unequal variances) or Mann–Whitney test for not normally distributed data.

Results

We observed a significant increase in the number of Lin-/VEGF-R2+ endothelial progenitor cells within the bone marrow in diabetic mice compared with non-diabetic mice. Two genes, SDF-1 and SELE, were significantly differentially expressed in diabetic Lin-/VEGF-R2+ endothelial progenitor cells and six other genes, CAV1, eNOS, CLDN5, NANOG, OCLN and BDNF, showed very low levels of expression in diabetic Lin-/VEGF-R2+ progenitor cells.

Conclusion

Low SDF-1 expression may contribute to the dysfunctional mobilization of bone marrow Lin-/VEGF-R2+ endothelial progenitor cells, which may contribute to microvascular injury in early diabetes.

Keywords:
Diabetes; Endothelial progenitor cells; Diabetic vasculopathies; Molecular pathology; SDF-1; Lin-/VEGF-R2+ EPCs; Cardiovascular pathology; Retinopathy