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Role of Scl39a13/ZIP13 in cardiovascular homeostasis

Zinc plays a critical role in many physiological processes, and disruption of zinc homeostasis induces various disorders, such as growth retardation, osteopenia, immune deficiency, and inflammation. However, how the imbalance in zinc homeostasis leads to heart disease is not yet fully understood. Ca...

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Autores principales: Hara, Takafumi, Yamada, Ikuko, Ohashi, Takuto, Tamura, Masaru, Hijikata, Atsushi, Watanabe, Takashi, Gao, Minghao, Ito, Kana, Kawamata, Saeko, Azuma, Shiori, Yoshigai, Emi, Sumiyoshi, Yukiko, Yasuhiro, Natsumi, Ohara, Osamu, dos Santos, Heloísa G., Fukada, Toshiyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9586387/
https://www.ncbi.nlm.nih.gov/pubmed/36269775
http://dx.doi.org/10.1371/journal.pone.0276452
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author Hara, Takafumi
Yamada, Ikuko
Ohashi, Takuto
Tamura, Masaru
Hijikata, Atsushi
Watanabe, Takashi
Gao, Minghao
Ito, Kana
Kawamata, Saeko
Azuma, Shiori
Yoshigai, Emi
Sumiyoshi, Yukiko
Yasuhiro, Natsumi
Ohara, Osamu
dos Santos, Heloísa G.
Fukada, Toshiyuki
author_facet Hara, Takafumi
Yamada, Ikuko
Ohashi, Takuto
Tamura, Masaru
Hijikata, Atsushi
Watanabe, Takashi
Gao, Minghao
Ito, Kana
Kawamata, Saeko
Azuma, Shiori
Yoshigai, Emi
Sumiyoshi, Yukiko
Yasuhiro, Natsumi
Ohara, Osamu
dos Santos, Heloísa G.
Fukada, Toshiyuki
author_sort Hara, Takafumi
collection PubMed
description Zinc plays a critical role in many physiological processes, and disruption of zinc homeostasis induces various disorders, such as growth retardation, osteopenia, immune deficiency, and inflammation. However, how the imbalance in zinc homeostasis leads to heart disease is not yet fully understood. Cardiovascular diseases are a major cause of death worldwide, and the development of novel therapeutic targets to treat it is urgently needed. We report that a zinc transporter, ZIP13, regulates cardiovascular homeostasis. We found that the expression level of Zip13 mRNA was diminished in both primary neonatal cardiomyocytes and mouse heart tissues treated with the cardiotoxic agent doxycycline. Primary neonatal cardiomyocytes from Zip13 gene-knockout (KO) mice exhibited abnormal irregular arrhythmic beating. RNA-seq analysis identified 606 differentially expressed genes in Zip13-KO mouse-derived primary neonatal cardiomyocytes and Gene ontology (GO) analysis revealed that both inflammation- and cell adhesion-related genes were significantly enriched. In addition, telemetry echocardiography analysis suggested that arrhythmias were likely to occur in Zip13-KO mice, in which elevated levels of the cardiac fibrosis marker Col1a1, vascular inflammation-related gene eNOS, and Golgi-related molecule GM130 were observed. These results indicate the physiological importance of ZIP13—it maintains cardiovascular homeostasis by resolving inflammation and stress response. Our findings suggest that optimizing ZIP13 expression and/or function may improve cardiovascular disease management.
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spelling pubmed-95863872022-10-22 Role of Scl39a13/ZIP13 in cardiovascular homeostasis Hara, Takafumi Yamada, Ikuko Ohashi, Takuto Tamura, Masaru Hijikata, Atsushi Watanabe, Takashi Gao, Minghao Ito, Kana Kawamata, Saeko Azuma, Shiori Yoshigai, Emi Sumiyoshi, Yukiko Yasuhiro, Natsumi Ohara, Osamu dos Santos, Heloísa G. Fukada, Toshiyuki PLoS One Research Article Zinc plays a critical role in many physiological processes, and disruption of zinc homeostasis induces various disorders, such as growth retardation, osteopenia, immune deficiency, and inflammation. However, how the imbalance in zinc homeostasis leads to heart disease is not yet fully understood. Cardiovascular diseases are a major cause of death worldwide, and the development of novel therapeutic targets to treat it is urgently needed. We report that a zinc transporter, ZIP13, regulates cardiovascular homeostasis. We found that the expression level of Zip13 mRNA was diminished in both primary neonatal cardiomyocytes and mouse heart tissues treated with the cardiotoxic agent doxycycline. Primary neonatal cardiomyocytes from Zip13 gene-knockout (KO) mice exhibited abnormal irregular arrhythmic beating. RNA-seq analysis identified 606 differentially expressed genes in Zip13-KO mouse-derived primary neonatal cardiomyocytes and Gene ontology (GO) analysis revealed that both inflammation- and cell adhesion-related genes were significantly enriched. In addition, telemetry echocardiography analysis suggested that arrhythmias were likely to occur in Zip13-KO mice, in which elevated levels of the cardiac fibrosis marker Col1a1, vascular inflammation-related gene eNOS, and Golgi-related molecule GM130 were observed. These results indicate the physiological importance of ZIP13—it maintains cardiovascular homeostasis by resolving inflammation and stress response. Our findings suggest that optimizing ZIP13 expression and/or function may improve cardiovascular disease management. Public Library of Science 2022-10-21 /pmc/articles/PMC9586387/ /pubmed/36269775 http://dx.doi.org/10.1371/journal.pone.0276452 Text en © 2022 Hara et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Hara, Takafumi
Yamada, Ikuko
Ohashi, Takuto
Tamura, Masaru
Hijikata, Atsushi
Watanabe, Takashi
Gao, Minghao
Ito, Kana
Kawamata, Saeko
Azuma, Shiori
Yoshigai, Emi
Sumiyoshi, Yukiko
Yasuhiro, Natsumi
Ohara, Osamu
dos Santos, Heloísa G.
Fukada, Toshiyuki
Role of Scl39a13/ZIP13 in cardiovascular homeostasis
title Role of Scl39a13/ZIP13 in cardiovascular homeostasis
title_full Role of Scl39a13/ZIP13 in cardiovascular homeostasis
title_fullStr Role of Scl39a13/ZIP13 in cardiovascular homeostasis
title_full_unstemmed Role of Scl39a13/ZIP13 in cardiovascular homeostasis
title_short Role of Scl39a13/ZIP13 in cardiovascular homeostasis
title_sort role of scl39a13/zip13 in cardiovascular homeostasis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9586387/
https://www.ncbi.nlm.nih.gov/pubmed/36269775
http://dx.doi.org/10.1371/journal.pone.0276452
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