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How many cadherins do human endothelial cells express?

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Abstract

The vasculature is the paradigm of a compartment generated by parallel cellular barriers that aims to transport oxygen, nutrients and immune cells in complex organisms. Vascular barrier dysfunction leads to fatal acute and chronic inflammatory diseases. The endothelial barrier lines the inner side of vessels and is the main regulator of vascular permeability. Cadherins comprise a superfamily of 114 calcium-dependent adhesion proteins that contain conserved cadherin motifs and form cell–cell junctions in metazoans. In mature human endothelial cells, only VE (vascular endothelial)-cadherin and N (neural)-cadherin have been investigated in detail. Although both cadherins are essential for regulating endothelial permeability, no comprehensive expression studies to identify which other family members could play a relevant role in endothelial cells has so far been performed. Here, we have reviewed gene and protein expression databases to analyze cadherin expression in mature human endothelium and found that at least 24 cadherin superfamily members are significantly expressed. Based on data obtained from other cell types, organisms and experimental models, we discuss their potential functions, many of them unrelated to the formation of endothelial cell–cell junctions. The expression of this new set of endothelial cadherins highlights the important but still poorly defined roles of planar cell polarity, the Hippo pathway and mitochondria metabolism in human vascular homeostasis.

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Abbreviations

APP:

Amyloid precursor protein

CCM:

Cerebral cavernous malformation

CDHR:

Cadherin-related proteins

CLSTN:

Calsyntenin

DCHS1:

Dachsous cadherin related 1

E-cadherin:

Epithelial cadherin

EMT:

Epithelial–mesenchymal transition

EndMT:

Endothelial–mesenchymal transition

GDNF:

Glial cell line-derived neurotrophic factor

GPI:

Glycosylphosphatidylinositol

HCV:

Hepatitis C virus

HUVEC:

Human umbilical vein endothelial cells

KSHV:

Kaposi ́s sarcoma-associated herpesvirus

MUCDHL:

Mucin and cadherin-like

N-cadherin:

Neural cadherin

OB-cadherin:

Osteoblast-cadherin

PCDH:

Protocadherin

PCDHG:

Protocadherin gamma (cluster)

PCP:

Planar cell polarity

phEndEC:

Primary human endoneurial endothelial cells

RET:

Rearranged during transfection

SMAD3:

Small and mothers against decapentaplegic 3

TGF- β:

Transforming growth factor-β

VE-cadherin:

Vascular endothelial cadherin

WNT:

Wingless-related integration site

YAP:

Yes-associated protein

TAZ:

Transcriptional coactivator with PDZ-binding motif

7D cadherin:

7-Domain cadherin

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Acknowledgments

We thank Cristina Cacho Navas and Dr. Nahuel Ramella for the critical reading of the manuscript and the Genomics Facility at the CBMSO for its helpful advice. We also thank Dr. Phil Mason, who provided English language support.

Funding

The work was supported by Grants SAF2017-88187-R from MINECO, B2017/BMD-3817 from Comunidad de Madrid and Endocornea 2, collaborative agreement with CSIC, funded by Instituto de Investigación Fundación Jiménez Díaz. N.C.A. is a recipient of an FPU fellowship from MECD.

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  1. Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, C/Nicolás Cabrera 1, Cantoblanco, 28049, Madrid, Spain

    Natalia Colás-Algora & Jaime Millán

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  1. Natalia Colás-Algora
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  2. Jaime Millán
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Correspondence to Jaime Millán.

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Colás-Algora, N., Millán, J. How many cadherins do human endothelial cells express?. Cell. Mol. Life Sci. 76, 1299–1317 (2019). https://doi.org/10.1007/s00018-018-2991-9

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  • DOI: https://doi.org/10.1007/s00018-018-2991-9

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