Format

Send to

Choose Destination
See comment in PubMed Commons below
J Cell Sci. 2014 Jun 15;127(Pt 12):2723-35. doi: 10.1242/jcs.143644. Epub 2014 Apr 28.

Expression of endoglin isoforms in the myeloid lineage and their role during aging and macrophage polarization.

Author information

1
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), 28040 Madrid, Spain Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 28040 Madrid, Spain.
2
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), 28040 Madrid, Spain.
3
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), 28040 Madrid, Spain Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 28040 Madrid, Spain bernabeu.c@cib.csic.es.

Abstract

Endoglin plays a crucial role in pathophysiological processes such as hereditary hemorrhagic telangiectasia (HHT), preeclampsia and cancer. Endoglin expression is upregulated during the monocyte-to-macrophage transition, but little is known about its regulation and function in these immune cells. Two different alternatively spliced isoforms of endoglin have been reported, L-endoglin and S-endoglin. Although L-endoglin is the predominant variant, here, we found that there was an increased expression of the S-endoglin isoform during senescence of the myeloid lineage in human and murine models. We performed a stable isotope labelling of amino acids in cell culture (SILAC) analysis of both L-endoglin and S-endoglin transfectants in the human promonocytic cell line U937. Analysis of differentially expressed protein clusters allowed the identification of cellular activities affected during aging. S-endoglin expression led to decreased cellular proliferation and a decreased survival response to granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced apoptosis, as well as increased oxidative stress. Gene expression and functional studies suggested that there was a non-redundant role for each endoglin isoform in monocyte biology. In addition, we found that S-endoglin impairs the monocytic differentiation into the pro-inflammatory M1 phenotype and contributes to the compromised status of macrophage functions during aging.

KEYWORDS:

Aging; Cellular senescence; Endoglin; Macrophage; Macrophage polarization; SILAC

PMID:
24777481
DOI:
10.1242/jcs.143644
[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Support Center