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Knockdown of FABP3 Impairs Cardiac Development in Zebrafish through the Retinoic Acid Signaling Pathway

Fatty acid-binding protein 3 (FABP3) is a member of the intracellular lipid-binding protein family, and is primarily expressed in cardiac muscle tissue. Previously, we found that FABP3 is highly expressed in patients with ventricular-septal defects and is often used as a plasma biomarker in idiopath...

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Autores principales: Wang, Xuejie, Zhou, Lijuan, Jin, Jin, Yang, Yang, Song, Guixian, Shen, Yahui, Liu, Hailang, Liu, Ming, Shi, Chunmei, Qian, Lingmei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Diversity Preservation International (MDPI) 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3742220/
https://www.ncbi.nlm.nih.gov/pubmed/23823803
http://dx.doi.org/10.3390/ijms140713826
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author Wang, Xuejie
Zhou, Lijuan
Jin, Jin
Yang, Yang
Song, Guixian
Shen, Yahui
Liu, Hailang
Liu, Ming
Shi, Chunmei
Qian, Lingmei
author_facet Wang, Xuejie
Zhou, Lijuan
Jin, Jin
Yang, Yang
Song, Guixian
Shen, Yahui
Liu, Hailang
Liu, Ming
Shi, Chunmei
Qian, Lingmei
author_sort Wang, Xuejie
collection PubMed
description Fatty acid-binding protein 3 (FABP3) is a member of the intracellular lipid-binding protein family, and is primarily expressed in cardiac muscle tissue. Previously, we found that FABP3 is highly expressed in patients with ventricular-septal defects and is often used as a plasma biomarker in idiopathic dilated cardiomyopathy, and may play a significant role in the development of these defects in humans. In the present study, we aimed to investigate the role of FABP3 in the embryonic development of the zebrafish heart, and specifically how morpholino (MO) mediated knockdown of FABP3 would affect heart development in this species. Our results revealed that knockdown of FABP3 caused significant impairment of cardiac development observed, including developmental delay, pericardial edema, a linear heart tube phenotype, incomplete cardiac loop formation, abnormal positioning of the ventricles and atria, downregulated expression of cardiac-specific markers and decreased heart rate. Mechanistically, our data showed that the retinoic acid (RA) catabolizing enzyme Cyp26a1 was upregulated in FABP3-MO zebrafish, as indicated by in situ hybridization and real-time PCR. On the other hand, the expression level of the RA synthesizing enzyme Raldh2 did not significantly change in FABP3-MO injected zebrafish. Collectively, our results indicated that FABP3 knockdown had significant effects on cardiac development, and that dysregulated RA signaling was one of the mechanisms underlying this effect. As a result, these studies identify FABP3 as a candidate gene underlying the etiology of congenital heart defects.
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spelling pubmed-37422202013-08-13 Knockdown of FABP3 Impairs Cardiac Development in Zebrafish through the Retinoic Acid Signaling Pathway Wang, Xuejie Zhou, Lijuan Jin, Jin Yang, Yang Song, Guixian Shen, Yahui Liu, Hailang Liu, Ming Shi, Chunmei Qian, Lingmei Int J Mol Sci Article Fatty acid-binding protein 3 (FABP3) is a member of the intracellular lipid-binding protein family, and is primarily expressed in cardiac muscle tissue. Previously, we found that FABP3 is highly expressed in patients with ventricular-septal defects and is often used as a plasma biomarker in idiopathic dilated cardiomyopathy, and may play a significant role in the development of these defects in humans. In the present study, we aimed to investigate the role of FABP3 in the embryonic development of the zebrafish heart, and specifically how morpholino (MO) mediated knockdown of FABP3 would affect heart development in this species. Our results revealed that knockdown of FABP3 caused significant impairment of cardiac development observed, including developmental delay, pericardial edema, a linear heart tube phenotype, incomplete cardiac loop formation, abnormal positioning of the ventricles and atria, downregulated expression of cardiac-specific markers and decreased heart rate. Mechanistically, our data showed that the retinoic acid (RA) catabolizing enzyme Cyp26a1 was upregulated in FABP3-MO zebrafish, as indicated by in situ hybridization and real-time PCR. On the other hand, the expression level of the RA synthesizing enzyme Raldh2 did not significantly change in FABP3-MO injected zebrafish. Collectively, our results indicated that FABP3 knockdown had significant effects on cardiac development, and that dysregulated RA signaling was one of the mechanisms underlying this effect. As a result, these studies identify FABP3 as a candidate gene underlying the etiology of congenital heart defects. Molecular Diversity Preservation International (MDPI) 2013-07-03 /pmc/articles/PMC3742220/ /pubmed/23823803 http://dx.doi.org/10.3390/ijms140713826 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland http://creativecommons.org/licenses/by/3.0 This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Wang, Xuejie
Zhou, Lijuan
Jin, Jin
Yang, Yang
Song, Guixian
Shen, Yahui
Liu, Hailang
Liu, Ming
Shi, Chunmei
Qian, Lingmei
Knockdown of FABP3 Impairs Cardiac Development in Zebrafish through the Retinoic Acid Signaling Pathway
title Knockdown of FABP3 Impairs Cardiac Development in Zebrafish through the Retinoic Acid Signaling Pathway
title_full Knockdown of FABP3 Impairs Cardiac Development in Zebrafish through the Retinoic Acid Signaling Pathway
title_fullStr Knockdown of FABP3 Impairs Cardiac Development in Zebrafish through the Retinoic Acid Signaling Pathway
title_full_unstemmed Knockdown of FABP3 Impairs Cardiac Development in Zebrafish through the Retinoic Acid Signaling Pathway
title_short Knockdown of FABP3 Impairs Cardiac Development in Zebrafish through the Retinoic Acid Signaling Pathway
title_sort knockdown of fabp3 impairs cardiac development in zebrafish through the retinoic acid signaling pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3742220/
https://www.ncbi.nlm.nih.gov/pubmed/23823803
http://dx.doi.org/10.3390/ijms140713826
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