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Family with Sequence Similarity 5, Member C (FAM5C) Increases Leukocyte Adhesion Molecules in Vascular Endothelial Cells: Implication in Vascular Inflammation

Identification of the regulators of vascular inflammation is important if we are to understand the molecular mechanisms leading to atherosclerosis and consequent ischemic heart disease, including acute myocardial infarction. Gene polymorphisms in family with sequence similarity 5, member C (FAM5C) a...

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Autores principales: Sato, Junya, Kinugasa, Mitsuo, Satomi-Kobayashi, Seimi, Hatakeyama, Kinta, Knox, Aaron J., Asada, Yujiro, Wierman, Margaret E., Hirata, Ken-ichi, Rikitake, Yoshiyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175995/
https://www.ncbi.nlm.nih.gov/pubmed/25251368
http://dx.doi.org/10.1371/journal.pone.0107236
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author Sato, Junya
Kinugasa, Mitsuo
Satomi-Kobayashi, Seimi
Hatakeyama, Kinta
Knox, Aaron J.
Asada, Yujiro
Wierman, Margaret E.
Hirata, Ken-ichi
Rikitake, Yoshiyuki
author_facet Sato, Junya
Kinugasa, Mitsuo
Satomi-Kobayashi, Seimi
Hatakeyama, Kinta
Knox, Aaron J.
Asada, Yujiro
Wierman, Margaret E.
Hirata, Ken-ichi
Rikitake, Yoshiyuki
author_sort Sato, Junya
collection PubMed
description Identification of the regulators of vascular inflammation is important if we are to understand the molecular mechanisms leading to atherosclerosis and consequent ischemic heart disease, including acute myocardial infarction. Gene polymorphisms in family with sequence similarity 5, member C (FAM5C) are associated with an increased risk of acute myocardial infarction, but little is known about the function of this gene product in blood vessels. Here, we report that the regulation of the expression and function of FAM5C in endothelial cells. We show here that FAM5C is expressed in endothelial cells in vitro and in vivo. Immunofluorescence microcopy showed localization of FAM5C in the Golgi in cultured human endothelial cells. Immunohistochemistry on serial sections of human coronary artery showed that FAM5C-positive endothelium expressed intercellular adhesion molecule-1 (ICAM-1) or vascular cell adhesion molecule-1 (VCAM-1). In cultured human endothelial cells, the overexpression of FAM5C increased the reactive oxygen species (ROS) production, nuclear factor-κB (NF-κB) activity and the expression of ICAM-1, VCAM-1 and E-selectin mRNAs, resulting in enhanced monocyte adhesion. FAM5C was upregulated in response to inflammatory stimuli, such as TNF-α, in an NF-κB- and JNK-dependent manner. Knockdown of FAM5C by small interfering RNA inhibited the increase in the TNF-α-induced production of ROS, NF-κB activity and expression of these leukocyte adhesion molecule mRNAs, resulting in reduced monocyte adhesion. These results suggest that in endothelial cells, when FAM5C is upregulated in response to inflammatory stimuli, it increases the expression of leukocyte adhesion molecules by increasing ROS production and NF-κB activity.
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spelling pubmed-41759952014-10-02 Family with Sequence Similarity 5, Member C (FAM5C) Increases Leukocyte Adhesion Molecules in Vascular Endothelial Cells: Implication in Vascular Inflammation Sato, Junya Kinugasa, Mitsuo Satomi-Kobayashi, Seimi Hatakeyama, Kinta Knox, Aaron J. Asada, Yujiro Wierman, Margaret E. Hirata, Ken-ichi Rikitake, Yoshiyuki PLoS One Research Article Identification of the regulators of vascular inflammation is important if we are to understand the molecular mechanisms leading to atherosclerosis and consequent ischemic heart disease, including acute myocardial infarction. Gene polymorphisms in family with sequence similarity 5, member C (FAM5C) are associated with an increased risk of acute myocardial infarction, but little is known about the function of this gene product in blood vessels. Here, we report that the regulation of the expression and function of FAM5C in endothelial cells. We show here that FAM5C is expressed in endothelial cells in vitro and in vivo. Immunofluorescence microcopy showed localization of FAM5C in the Golgi in cultured human endothelial cells. Immunohistochemistry on serial sections of human coronary artery showed that FAM5C-positive endothelium expressed intercellular adhesion molecule-1 (ICAM-1) or vascular cell adhesion molecule-1 (VCAM-1). In cultured human endothelial cells, the overexpression of FAM5C increased the reactive oxygen species (ROS) production, nuclear factor-κB (NF-κB) activity and the expression of ICAM-1, VCAM-1 and E-selectin mRNAs, resulting in enhanced monocyte adhesion. FAM5C was upregulated in response to inflammatory stimuli, such as TNF-α, in an NF-κB- and JNK-dependent manner. Knockdown of FAM5C by small interfering RNA inhibited the increase in the TNF-α-induced production of ROS, NF-κB activity and expression of these leukocyte adhesion molecule mRNAs, resulting in reduced monocyte adhesion. These results suggest that in endothelial cells, when FAM5C is upregulated in response to inflammatory stimuli, it increases the expression of leukocyte adhesion molecules by increasing ROS production and NF-κB activity. Public Library of Science 2014-09-24 /pmc/articles/PMC4175995/ /pubmed/25251368 http://dx.doi.org/10.1371/journal.pone.0107236 Text en © 2014 Sato et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Sato, Junya
Kinugasa, Mitsuo
Satomi-Kobayashi, Seimi
Hatakeyama, Kinta
Knox, Aaron J.
Asada, Yujiro
Wierman, Margaret E.
Hirata, Ken-ichi
Rikitake, Yoshiyuki
Family with Sequence Similarity 5, Member C (FAM5C) Increases Leukocyte Adhesion Molecules in Vascular Endothelial Cells: Implication in Vascular Inflammation
title Family with Sequence Similarity 5, Member C (FAM5C) Increases Leukocyte Adhesion Molecules in Vascular Endothelial Cells: Implication in Vascular Inflammation
title_full Family with Sequence Similarity 5, Member C (FAM5C) Increases Leukocyte Adhesion Molecules in Vascular Endothelial Cells: Implication in Vascular Inflammation
title_fullStr Family with Sequence Similarity 5, Member C (FAM5C) Increases Leukocyte Adhesion Molecules in Vascular Endothelial Cells: Implication in Vascular Inflammation
title_full_unstemmed Family with Sequence Similarity 5, Member C (FAM5C) Increases Leukocyte Adhesion Molecules in Vascular Endothelial Cells: Implication in Vascular Inflammation
title_short Family with Sequence Similarity 5, Member C (FAM5C) Increases Leukocyte Adhesion Molecules in Vascular Endothelial Cells: Implication in Vascular Inflammation
title_sort family with sequence similarity 5, member c (fam5c) increases leukocyte adhesion molecules in vascular endothelial cells: implication in vascular inflammation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175995/
https://www.ncbi.nlm.nih.gov/pubmed/25251368
http://dx.doi.org/10.1371/journal.pone.0107236
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