title: Genome-wide transcriptional and functional analysis of endoglin isoforms in the human promonocytic cell line U937.
abstract: Endoglin is an auxiliary cell surface receptor for TGF-β family members. Two different alternatively spliced isoforms, long (L)-endoglin and short (S)-endoglin, have been reported. S-endoglin and L-endoglin proteins vary from each other in their cytoplasmic tails that contain 14 and 47 amino acids, respectively. A critical role for endoglin in vascular development has primarily been studied in endothelial cells. In addition, endoglin expression is upregulated during monocyte-to-macrophage differentiation; however, little is known about its role in this myeloid context. To investigate the function of endoglin in monocytes, stable transfectants expressing the two endoglin isoforms in the promonocytic human cell line U937 were generated. The differential gene expression fingerprinting of these endoglin transfectants using DNA microarrays and further bioinformatics analysis showed a clear alteration in essential biological functions, mainly those related to "Cellular Movement", including cell adhesion and transmigration. Interestingly, these cellular functions are highly dependent on adhesion molecules, including integrins α1 (CD49a, ITGA1 gene), αL (CD11a, ITGAL gene), αM (CD11b, ITGAM gene) and β2 (CD18, ITGB2 gene) and the chemokine receptor CCR2 (CD192, CCR2 gene), which are downregulated in endoglin transfectants. Moreover, activin A (INHBA gene), a TGF-β superfamily member involved in macrophage polarization, was distinctly affected in each endoglin transfectant, and may contribute to the regulated expression of integrins. These data were confirmed by quantitative PCR, flow cytometry and functional tests. Taken together, these results provide new insight into endoglin function in monocytes.
authors.affiliation: Department of Cellular and Molecular Medicine, Centro de Investigaciones Biologicas, Consejo Superior de Investigaciones Cientificas (CSIC) and Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Blanco
authors.forename: Luisa
authors.initials: L
authors.lastname: Ojeda-Fernandez
authors.forename: Mikel
authors.initials: M
authors.lastname: Aristorena
authors.forename: Eunate
authors.initials: E
authors.lastname: Gallardo-Vara
authors.forename: Alberto
authors.initials: A
authors.lastname: Benguria
authors.forename: Ana
authors.initials: A
authors.lastname: Dopazo
authors.forename: Carmen
authors.initials: C
authors.lastname: Langa
authors.forename: Luisa M
authors.initials: LM
authors.lastname: Botella
authors.forename: Carmelo
authors.initials: C
authors.lastname: Bernabeu
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D000071063:Endoglin; D042783:Endothelial Cells / Q000378:metabolism; D055106:Genome-Wide Association Study; D006801:Humans; D016023:Integrins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D051379:Mice; D009000:Monocytes / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D020298:U937 Cells
chemical_list: D015703:Antigens, CD; D015815:Cell Adhesion Molecules; C064206:ENG protein, human; D000071063:Endoglin; C502004:Eng protein, mouse; D016023:Integrins; D047908:Intracellular Signaling Peptides and Proteins; D020033:Protein Isoforms; D011956:Receptors, Cell Surface; D016212:Transforming Growth Factor beta