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Type: Journal article
Title: A non-canonical role for desmoglein-2 in endothelial cells: implications for neoangiogenesis
Author: Ebert, L.
Tan, L.
Johan, M.
Min, K.
Cockshell, M.
Parham, K.
Betterman, K.
Szeto, P.
Boyle, S.
Silva, L.
Peng, A.
Zhang, Y.
Ruszkiewicz, A.
Zannettino, A.
Gronthos, S.
Koblar, S.
Harvey, N.
Lopez, A.
Shackleton, M.
Bonder, C.
Citation: Angiogenesis, 2016; 19(4):463-486
Publisher: Springer
Issue Date: 2016
ISSN: 0969-6970
Statement of
Lisa M. Ebert, Lih Y. Tan, M. Zahied Johan, Kay Khine Myo Min, Michaelia P. Cockshell, Kate A. Parham, Kelly L. Betterman, Paceman Szeto, Samantha Boyle, Lokugan Silva, Angela Peng, YouFang Zhang, Andrew Ruszkiewicz, Andrew C. W. Zannettino, Stan Gronthos, Simon Koblar, Natasha L. Harvey, Angel F. Lopez, Mark Shackleton, Claudine S. Bonder
Abstract: Desmogleins (DSG) are a family of cadherin adhesion proteins that were first identified in desmosomes and provide cardiomyocytes and epithelial cells with the junctional stability to tolerate mechanical stress. However, one member of this family, DSG2, is emerging as a protein with additional biological functions on a broader range of cells. Here we reveal that DSG2 is expressed by nondesmosome- forming human endothelial progenitor cells as well as their mature counterparts [endothelial cells (ECs)] in human tissue from healthy individuals and cancer patients. Analysis of normal blood and bone marrow showed that DSG2 is also expressed by CD34?CD45dim hematopoietic progenitor cells. An inability to detect other desmosomal components, i.e., DSG1, DSG3 and desmocollin (DSC)2/3, on these cells supports a solitary role for DSG2 outside of desmosomes. Functionally, we show that CD34?CD45dimDSG2? progenitor cells are multi-potent and pro-angiogenic in vitro. Using a ‘knockout-first’ approach, we generated a Dsg2 loss-of-function strain of mice (Dsg2lo/lo) and observed that, in response to reduced levels of Dsg2: (i) CD31? ECs in the pancreas are hypertrophic and exhibit altered morphology, (ii) bone marrowderived endothelial colony formation is impaired, (iii) ex vivo vascular sprouting from aortic rings is reduced, and (iv) vessel formation in vitro and in vivo is attenuated. Finally, knockdown of DSG2 in a human bone marrow EC line reveals a reduction in an in vitro angiogenesis assay as well as relocalisation of actin and VE-cadherin away from the cell junctions, reduced cell–cell adhesion and increased invasive properties by these cells. In summary, we have identified DSG2 expression in distinct progenitor cell subpopulations and show that, independent from its classical function as a component of desmosomes, this cadherin also plays a critical role in the vasculature.
Keywords: DESMOGLEIN-2; Endothelial progenitor cells; Endothelium; Hematopoietic stem and progenitor cells; Mouse models of neoangiogenesis
Rights: © The Author(s) 2016. This article is published with open access at Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://crea, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
RMID: 0030050436
DOI: 10.1007/s10456-016-9520-y
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