NDLI: A non-canonical role for desmoglein-2 in endothelial cells: implications for neoangiogenesis

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A non-canonical role for desmoglein-2 in endothelial cells: implications for neoangiogenesis

Content Provider	Springer Nature Link
Author	Ebert, Lisa M. Tan, Lih Y. Johan, M. Zahied Min, Kay Khine Myo Cockshell, Michaelia P. Parham, Kate A. Betterman, Kelly L. Szeto, Paceman Boyle, Samantha Silva, Lokugan Peng, Angela Zhang, YouFang Ruszkiewicz, Andrew Zannetti, Andrew C. W. Gronthos, Stan Koblar, Simon Harvey, Natasha L. Lopez, Angel F. Shackleton, Mark Bonder, Claudine S.
Copyright Year	2016
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 non-desmosome-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 (Dsg2 lo/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 marrow-derived 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.
Starting Page	463
Ending Page	486
Page Count	24
File Format	PDF
ISSN	09696970
Journal	Angiogenesis
Volume Number	19
Issue Number	4
e-ISSN	15737209
Language	English
Publisher	Springer Netherlands
Publisher Date	2016-06-23
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	DESMOGLEIN-2 Endothelial progenitor cells Endothelium Hematopoietic stem and progenitor cells Mouse models of neoangiogenesis Cancer Research Biomedicine general Cell Biology Cardiology Ophthalmology Oncology
Content Type	Text
Resource Type	Article
Subject	Physiology Clinical Biochemistry Cancer Research

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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A non-canonical role for desmoglein-2 in endothelial cells: implications for neoangiogenesis

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