Expression of endoglin isoforms in the myeloid lineage and their role during aging and macrophage polarization.
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.
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.
Mikel
M
Aristorena
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.
Francisco J
FJ
Blanco
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), 28040 Madrid, Spain.
Mateo
M
de Las Casas-Engel
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.
Luisa
L
Ojeda-Fernandez
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.
Eunate
E
Gallardo-Vara
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), 28040 Madrid, Spain.
Angel
A
Corbi
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.
Luisa M
LM
Botella
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.
Carmelo
C
Bernabeu
D017398:Alternative Splicing; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D016764:Cell Polarity; D016922:Cellular Senescence; D000071063:Endoglin; D015870:Gene Expression; D006801:Humans; D008264:Macrophages / Q000502:physiology*; D009000:Monocytes / Q000502:physiology; D018384:Oxidative Stress; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*
D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D020033:Protein Isoforms; D011956:Receptors, Cell Surface
Aging; Cellular senescence; Endoglin; Macrophage; Macrophage polarization; SILAC