miR126-5p repression of ALCAM and SetD5 in endothelial cells regulates leucocyte adhesion and transmigration

Poissonnier, Loïc; Villain, Gaëlle; Soncin, Fabrice; Mattot, Virginie

doi:10.1093/cvr/cvu040

Cited by 48 publications

(47 citation statements)

References 40 publications

(44 reference statements)

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“…Lymphocyte extravasation is a multistep process that involves rolling, adhesion, and transmigration (42). ALCAM does not directly participate in leukocyte adhesion to endothelium in a model consisting of THP-1 monocytes interacting with human umbilical vein endothelial cells (HUVECs) (15). However, ALCAM regulates actin dynamics during the lymphocyte-endothelium cross talk (43,44).…”

Section: Discussionmentioning

confidence: 99%

“…ALCAM is expressed on endothelia and epithelia, where it participates in tissue development and maintenance (13); CD6 is not expressed on endothelia (14). ALCAM downregulation on primary human umbilical vein endothelial cells reduces monocyte transmigration (15). Conversely, ALCAM overexpression on endothelia or epithelia usually enhances cell extravasation and metastasis (14,16).…”

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confidence: 99%

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Human T-Lymphotropic Virus Type 1-Induced Overexpression of Activated Leukocyte Cell Adhesion Molecule (ALCAM) Facilitates Trafficking of Infected Lymphocytes through the Blood-Brain Barrier

Curis

Percher

Jeannin

et al. 2016

J Virol

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Human T-Lymphotropic Virus Type 1-Induced Overexpression of Activated Leukocyte Cell Adhesion Molecule (ALCAM) Facilitates Trafficking of Infected Lymphocytes through the Blood-Brain Barrier

Curis

Percher

Jeannin

et al. 2016

J Virol

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“…Isolation of CD31 ϩ Cells-CD31ϩ cells were purified from mouse lungs using anti-CD31-coated magnetic Dynabeads (Life Technologies) exactly as described in (23).…”

Section: Methodsmentioning

confidence: 99%

“…5A). This point was particularly important because miR126-3p and miR126-5p are embedded within the egfl7 gene seventh intron, and both are known to affect endothelial cell activation (22,23). The effects of siEgfl7 in HUVEC could be rescued by overexpressing Egfl7 by the means of an expression plasmid.…”

Section: Tnf␣-induced Endothelial Cell Activation Is Repressed By Endmentioning

confidence: 99%

Endothelial Cell Activation Is Regulated by Epidermal Growth Factor-like Domain 7 (Egfl7) during Inflammation

Pinte

Caetano

Bras

et al. 2016

Journal of Biological Chemistry

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Edited by Dennis VoelkerActivation of the blood vessel endothelium is a critical step during inflammation. Endothelial cells stimulated by pro-inflammatory cytokines play an essential part in the adhesion and extravasation of circulating leukocytes into inflamed tissues. The endothelial egfl7 gene (VE-statin) represses endothelial cell activation in tumors, and prior observations suggested that it could also participate in the regulation of endothelial cell activation during inflammation. We show here that Egfl7 expression is strongly repressed in mouse lung endothelial cells during LPS-and TNF␣-induced inflammation in vivo. LPS have a limited effect on Egfl7 expression by endothelial cells in vitro, whereas the pro-inflammatory cytokine TNF␣ strongly represses Egfl7 expression in endothelial cells. TNF␣ regulates the egfl7 gene promoter through regions located between ؊7585 and ؊5550 bp ahead of the main transcription start site and via an NF-B-dependent mechanism. Conversely, Egfl7 regulates the response of endothelial cells to TNF␣ by restraining the induced expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin, resulting in a decreased adhesion of leukocytes onto endothelial cells stimulated by TNF␣. Egfl7 regulates the expression of these adhesion molecules through the NF-B and MEK/Erk pathways, in particular by preventing the proteasomemediated degradation of IkB␣ both in non-activated endothelial cells and during activation. Egfl7 is thus an endogenous and constitutive repressor of blood vessel endothelial cell activation in normal and inflammatory conditions and participates in a loop of regulation of activation of these cells by pro-inflammatory cytokines.Endothelial cells line the luminal side of blood vessels in direct contact with the circulation. Under normal conditions, the endothelium forms a non-adhesive and non-thrombogenic surface on which blood cells slide with minimal interactions with the vascular wall. During inflammation, endothelial cells become activated in response to pro-inflammatory cytokines, which promote a strong increase in the expression levels of leukocyte adhesion molecules such as E-selectin, intercellular adhesion molecule-1 (ICAM-1), 4 and vascular cell adhesion molecule-1 (VCAM-1). These adhesion molecules are expressed at the endothelial cell surface and participate in the rolling, arrest, firm adhesion, and extravasation of immune cells from the circulation through the endothelium and toward the tissues (1). Endothelial cell activation in response to inflammation and its subsequent capture of leukocytes is thus a vital response, and its regulation is critical. Excessive or aberrant local activation of endothelial cells leads to inflammatory disorders such as atherosclerosis, chronic inflammation, multiple sclerosis, and rheumatoid arthritis. Activation of the endothelium is transitory, and endothelial cells resume a basal, nonactivated condition when pro-inflammatory cytokines levels recess. Thus, most of the ...

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“…Similar to other coding genes, ALCAM works as the downstream target gene of miRNAs. Previous studies showed that ALCAM is regulated by miR-9, miR-483-5p and miR-126-5p and always relevant to invasive behavior in different tumors [26-28]. While, if ALCAM regulates the proliferation and invasion capacity of PAs cells and is regulated by miRNAs still remains unknown.…”

Section: Introductionmentioning

confidence: 99%

MiR-148b, MiR-152/ALCAM Axis Regulates the Proliferation and Invasion of Pituitary Adenomas Cells

Huang

et al. 2017

Cell Physiol Biochem

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Background/Aims: Aberrant expression of miRNA has been found in many tumor tissues to regulate the tumorigenesis by binding to the 3`- untranslated region (3`-UTR) of the target genes. The aim of this study is to investigate the role of miR-148b, miR-152/ALCAM axis in human pituitary adenomas (PAs). Methods: First, we detected the expression level of miR-148b-3p and miR-152 in human PAs samples by using qRT-PCR. Then we studied the role of miR-148b-3p, miR-152 on human PAs cell proliferation, invasion and apoptosis by using MTS assay, Transwell invasion assay and Annexin V/PI Staining Test. To study the relationship between miR-148b-3p, miR-152 and activated leukocyte antigen molecule (ALCAM), we overexpressed miR-148-3p or miR-152 by transfecting specific mimics. Lucifearase reporter assay was then performed to confirm the target. Next, we studied the biological functions of ALCAM in human PAs cells. Finally, the role of miR-148b-3p, miR-152/ALCAM axis in PAs cells was studied. Results: The expression level of miR-148-3p and miR-152 in invasive PAs samples was lower than those in noninvasive samples. Overexpression of miR-148b-3p, miR-152 could repress proliferation and invasion, and promote apoptosis. Moreover, miR-148b-3p and miR-152 could repress activated leukocyte antigen molecule (ALCAM) expression. Knockdown of ALCAM could repress proliferation and invasion and promote apoptosis. By contrary, overexpression of ALCAM promoted proliferation and invasion. Further, the rescue experiments indicated that overexpression of ALCAM significantly restored the proliferation, apoptosis, and invasion influenced by miR-148b-3p and miR-152. Conclusions: Our study suggests that miR-148b-3p, miR-152 may serve as suppressors in PAs through downregulating ALCAM expression. miR-148b, miR-152/ ALCAM axis may be a new therapeutic target in the future.

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miR126-5p repression of ALCAM and SetD5 in endothelial cells regulates leucocyte adhesion and transmigration

Abstract: miR126-5p is a functional, endothelial-enriched microRNA that participates in the control of leucocyte trafficking by regulating the expression of ALCAM and SetD5.

Cited by 48 publications

References 40 publications

Human T-Lymphotropic Virus Type 1-Induced Overexpression of Activated Leukocyte Cell Adhesion Molecule (ALCAM) Facilitates Trafficking of Infected Lymphocytes through the Blood-Brain Barrier

Human T-Lymphotropic Virus Type 1-Induced Overexpression of Activated Leukocyte Cell Adhesion Molecule (ALCAM) Facilitates Trafficking of Infected Lymphocytes through the Blood-Brain Barrier

Endothelial Cell Activation Is Regulated by Epidermal Growth Factor-like Domain 7 (Egfl7) during Inflammation

MiR-148b, MiR-152/ALCAM Axis Regulates the Proliferation and Invasion of Pituitary Adenomas Cells

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