Anoxia Rapidly Induces Changes in Expression of a Large and Diverse Set of Genes in Endothelial Cells

Sinusoidal endothelial cells are the predominant vascular surface of the bone marrow and constitute the functional hematopoietic niche where hematopoietic stem and progenitor cells receive cues for self-renewal, survival, and differentiation. In the bone marrow hematopoietic niche, the oxygen tensio...

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Main Authors: Antonella Antonelli, Emanuele Salvatore Scarpa, Santina Bruzzone, Cecilia Astigiano, Francesco Piacente, Michela Bruschi, Alessandra Fraternale, Christian A. Di Buduo, Alessandra Balduini, Mauro Magnani
Format: Article
Language:English
Published: MDPI AG 2023-03-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/6/5157
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author Antonella Antonelli
Emanuele Salvatore Scarpa
Santina Bruzzone
Cecilia Astigiano
Francesco Piacente
Michela Bruschi
Alessandra Fraternale
Christian A. Di Buduo
Alessandra Balduini
Mauro Magnani
author_facet Antonella Antonelli
Emanuele Salvatore Scarpa
Santina Bruzzone
Cecilia Astigiano
Francesco Piacente
Michela Bruschi
Alessandra Fraternale
Christian A. Di Buduo
Alessandra Balduini
Mauro Magnani
author_sort Antonella Antonelli
collection DOAJ
description Sinusoidal endothelial cells are the predominant vascular surface of the bone marrow and constitute the functional hematopoietic niche where hematopoietic stem and progenitor cells receive cues for self-renewal, survival, and differentiation. In the bone marrow hematopoietic niche, the oxygen tension is usually very low, and this condition affects stem and progenitor cell proliferation and differentiation and other important functions of this region. Here, we have investigated in vitro the response of endothelial cells to a marked decrease in O<sub>2</sub> partial pressure to understand how the basal gene expression of some relevant biological factors (i.e., chemokines and interleukins) that are fundamental for the intercellular communication could change in anoxic conditions. Interestingly, mRNA levels of <i>CXCL3</i>, <i>CXCL5</i>, and <i>IL-34</i> genes are upregulated after anoxia exposure but become downmodulated by sirtuin 6 (SIRT6) overexpression. Indeed, the expression levels of some other genes (such as <i>Leukemia Inhibitory Factor</i> (<i>LIF</i>)) that were not significantly affected by 8 h anoxia exposure become upregulated in the presence of SIRT6. Therefore, SIRT6 mediates also the endothelial cellular response through the modulation of selected genes in an extreme hypoxic condition.
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spelling doaj.art-d0755413f10849259974c74ef0d754602023-11-17T11:29:54ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01246515710.3390/ijms24065157Anoxia Rapidly Induces Changes in Expression of a Large and Diverse Set of Genes in Endothelial CellsAntonella Antonelli0Emanuele Salvatore Scarpa1Santina Bruzzone2Cecilia Astigiano3Francesco Piacente4Michela Bruschi5Alessandra Fraternale6Christian A. Di Buduo7Alessandra Balduini8Mauro Magnani9Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, ItalyDepartment of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, ItalyDepartment of Experimental Medicine, Section of Biochemistry, Viale Benedetto XV 1, 16132 Genova, ItalyDepartment of Experimental Medicine, Section of Biochemistry, Viale Benedetto XV 1, 16132 Genova, ItalyDepartment of Experimental Medicine, Section of Biochemistry, Viale Benedetto XV 1, 16132 Genova, ItalyDepartment of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, ItalyDepartment of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, ItalyDepartment of Molecular Medicine, University of Pavia, 27100 Pavia, ItalyDepartment of Molecular Medicine, University of Pavia, 27100 Pavia, ItalyDepartment of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, ItalySinusoidal endothelial cells are the predominant vascular surface of the bone marrow and constitute the functional hematopoietic niche where hematopoietic stem and progenitor cells receive cues for self-renewal, survival, and differentiation. In the bone marrow hematopoietic niche, the oxygen tension is usually very low, and this condition affects stem and progenitor cell proliferation and differentiation and other important functions of this region. Here, we have investigated in vitro the response of endothelial cells to a marked decrease in O<sub>2</sub> partial pressure to understand how the basal gene expression of some relevant biological factors (i.e., chemokines and interleukins) that are fundamental for the intercellular communication could change in anoxic conditions. Interestingly, mRNA levels of <i>CXCL3</i>, <i>CXCL5</i>, and <i>IL-34</i> genes are upregulated after anoxia exposure but become downmodulated by sirtuin 6 (SIRT6) overexpression. Indeed, the expression levels of some other genes (such as <i>Leukemia Inhibitory Factor</i> (<i>LIF</i>)) that were not significantly affected by 8 h anoxia exposure become upregulated in the presence of SIRT6. Therefore, SIRT6 mediates also the endothelial cellular response through the modulation of selected genes in an extreme hypoxic condition.https://www.mdpi.com/1422-0067/24/6/5157anoxiaendothelial cellsinterleukin/cytokine expressiontranscriptome analysisSIRT6
spellingShingle Antonella Antonelli
Emanuele Salvatore Scarpa
Santina Bruzzone
Cecilia Astigiano
Francesco Piacente
Michela Bruschi
Alessandra Fraternale
Christian A. Di Buduo
Alessandra Balduini
Mauro Magnani
Anoxia Rapidly Induces Changes in Expression of a Large and Diverse Set of Genes in Endothelial Cells
International Journal of Molecular Sciences
anoxia
endothelial cells
interleukin/cytokine expression
transcriptome analysis
SIRT6
title Anoxia Rapidly Induces Changes in Expression of a Large and Diverse Set of Genes in Endothelial Cells
title_full Anoxia Rapidly Induces Changes in Expression of a Large and Diverse Set of Genes in Endothelial Cells
title_fullStr Anoxia Rapidly Induces Changes in Expression of a Large and Diverse Set of Genes in Endothelial Cells
title_full_unstemmed Anoxia Rapidly Induces Changes in Expression of a Large and Diverse Set of Genes in Endothelial Cells
title_short Anoxia Rapidly Induces Changes in Expression of a Large and Diverse Set of Genes in Endothelial Cells
title_sort anoxia rapidly induces changes in expression of a large and diverse set of genes in endothelial cells
topic anoxia
endothelial cells
interleukin/cytokine expression
transcriptome analysis
SIRT6
url https://www.mdpi.com/1422-0067/24/6/5157
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