Melanocytes determine angiogenesis gene expression across human tissues.

Several angiogenesis-dependent diseases, including age-related macular degeneration and infantile hemangioma, display differential prevalence among Black, as compared to White individuals. Although socioeconomic status and genetic architecture have been suggested as explaining these differences, we...

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Autores principales: Shirly Freilikhman, Marianna Halasi, Alal Eran, Irit Adini
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Publicado: Public Library of Science (PLoS) 2021
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Acceso en línea:https://doaj.org/article/34f0957fb4c04fdcad9cb055a2a86c09
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spelling oai:doaj.org-article:34f0957fb4c04fdcad9cb055a2a86c092021-12-02T20:05:36ZMelanocytes determine angiogenesis gene expression across human tissues.1932-620310.1371/journal.pone.0251121https://doaj.org/article/34f0957fb4c04fdcad9cb055a2a86c092021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0251121https://doaj.org/toc/1932-6203Several angiogenesis-dependent diseases, including age-related macular degeneration and infantile hemangioma, display differential prevalence among Black, as compared to White individuals. Although socioeconomic status and genetic architecture have been suggested as explaining these differences, we have recently shown that pigment production per se might be involved. For example, we have shown that the extracellular protein fibromodulin is a pro-angiogenic factor highly secreted by melanocytes in White but not Black individuals. Still, additional pigment-dependent angiogenic factors and their molecular mechanisms remain to be identified. Understanding the contribution of pigmentation to angiogenesis in health and disease is essential for precision medicine of angiogenesis-dependent diseases with racial disparity. Toward that goal, we compared the transcriptomes of Black and White individuals in three tissues with angiogenic activity, namely artery, whole blood, and skin. We identified several differentially expressed angiogenesis pathways, including artery morphogenesis, regulation of endothelial cell chemotaxis, and cellular response to vascular endothelial growth factor stimulus. We then demonstrated that the expression of key genes in these pathways is directly modulated by the degree of pigmentation. We further identified the precise pigment production pathway controlling the expression of these genes, namely melanocortin 1 receptor (MC1R) signaling. These results demonstrate pigment-mediated regulation of angiogenesis-related pathways and their driver genes across human tissues.Shirly FreilikhmanMarianna HalasiAlal EranIrit AdiniPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 5, p e0251121 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Shirly Freilikhman
Marianna Halasi
Alal Eran
Irit Adini
Melanocytes determine angiogenesis gene expression across human tissues.
description Several angiogenesis-dependent diseases, including age-related macular degeneration and infantile hemangioma, display differential prevalence among Black, as compared to White individuals. Although socioeconomic status and genetic architecture have been suggested as explaining these differences, we have recently shown that pigment production per se might be involved. For example, we have shown that the extracellular protein fibromodulin is a pro-angiogenic factor highly secreted by melanocytes in White but not Black individuals. Still, additional pigment-dependent angiogenic factors and their molecular mechanisms remain to be identified. Understanding the contribution of pigmentation to angiogenesis in health and disease is essential for precision medicine of angiogenesis-dependent diseases with racial disparity. Toward that goal, we compared the transcriptomes of Black and White individuals in three tissues with angiogenic activity, namely artery, whole blood, and skin. We identified several differentially expressed angiogenesis pathways, including artery morphogenesis, regulation of endothelial cell chemotaxis, and cellular response to vascular endothelial growth factor stimulus. We then demonstrated that the expression of key genes in these pathways is directly modulated by the degree of pigmentation. We further identified the precise pigment production pathway controlling the expression of these genes, namely melanocortin 1 receptor (MC1R) signaling. These results demonstrate pigment-mediated regulation of angiogenesis-related pathways and their driver genes across human tissues.
format article
author Shirly Freilikhman
Marianna Halasi
Alal Eran
Irit Adini
author_facet Shirly Freilikhman
Marianna Halasi
Alal Eran
Irit Adini
author_sort Shirly Freilikhman
title Melanocytes determine angiogenesis gene expression across human tissues.
title_short Melanocytes determine angiogenesis gene expression across human tissues.
title_full Melanocytes determine angiogenesis gene expression across human tissues.
title_fullStr Melanocytes determine angiogenesis gene expression across human tissues.
title_full_unstemmed Melanocytes determine angiogenesis gene expression across human tissues.
title_sort melanocytes determine angiogenesis gene expression across human tissues.
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/34f0957fb4c04fdcad9cb055a2a86c09
work_keys_str_mv AT shirlyfreilikhman melanocytesdetermineangiogenesisgeneexpressionacrosshumantissues
AT mariannahalasi melanocytesdetermineangiogenesisgeneexpressionacrosshumantissues
AT alaleran melanocytesdetermineangiogenesisgeneexpressionacrosshumantissues
AT iritadini melanocytesdetermineangiogenesisgeneexpressionacrosshumantissues
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