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Protein tyrosine phosphatase receptor-ζ1 deletion triggers defective heart morphogenesis in mice and zebrafish
Protein tyrosine phosphatase receptor-ζ1 (PTPRZ1) is a transmembrane tyrosine phosphatase receptor highly expressed in embryonic stem cells. In the present work, gene expression analyses of Ptprz1(−/−) and Ptprz1(+/+) mice endothelial cells and hearts pointed to an unidentified role of PTPRZ1 in hea...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Physiological Society
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8754060/ https://www.ncbi.nlm.nih.gov/pubmed/34767486 http://dx.doi.org/10.1152/ajpheart.00400.2021 |
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author | Katraki-Pavlou, Stamatiki Kastana, Pinelopi Bousis, Dimitris Ntenekou, Despoina Varela, Aimilia Davos, Constantinos H. Nikou, Sophia Papadaki, Eleni Tsigkas, Grigorios Athanasiadis, Emmanouil Herradon, Gonzalo Mikelis, Constantinos M. Beis, Dimitris Papadimitriou, Evangelia |
author_facet | Katraki-Pavlou, Stamatiki Kastana, Pinelopi Bousis, Dimitris Ntenekou, Despoina Varela, Aimilia Davos, Constantinos H. Nikou, Sophia Papadaki, Eleni Tsigkas, Grigorios Athanasiadis, Emmanouil Herradon, Gonzalo Mikelis, Constantinos M. Beis, Dimitris Papadimitriou, Evangelia |
author_sort | Katraki-Pavlou, Stamatiki |
collection | PubMed |
description | Protein tyrosine phosphatase receptor-ζ1 (PTPRZ1) is a transmembrane tyrosine phosphatase receptor highly expressed in embryonic stem cells. In the present work, gene expression analyses of Ptprz1(−/−) and Ptprz1(+/+) mice endothelial cells and hearts pointed to an unidentified role of PTPRZ1 in heart development through the regulation of heart-specific transcription factor genes. Echocardiography analysis in mice identified that both systolic and diastolic functions are affected in Ptprz1(−/−) compared with Ptprz1(+/+) hearts, based on a dilated left ventricular (LV) cavity, decreased ejection fraction and fraction shortening, and increased angiogenesis in Ptprz1(−/−) hearts, with no signs of cardiac hypertrophy. A zebrafish ptprz1(−/−) knockout was also generated and exhibited misregulated expression of developmental cardiac markers, bradycardia, and defective heart morphogenesis characterized by enlarged ventricles and defected contractility. A selective PTPRZ1 tyrosine phosphatase inhibitor affected zebrafish heart development and function in a way like what is observed in the ptprz1(−/−) zebrafish. The same inhibitor had no effect in the function of the adult zebrafish heart, suggesting that PTPRZ1 is not important for the adult heart function, in line with data from the human cell atlas showing very low to negligible PTPRZ1 expression in the adult human heart. However, in line with the animal models, Ptprz1 was expressed in many different cell types in the human fetal heart, such as valvar, fibroblast-like, cardiomyocytes, and endothelial cells. Collectively, these data suggest that PTPRZ1 regulates cardiac morphogenesis in a way that subsequently affects heart function and warrant further studies for the involvement of PTPRZ1 in idiopathic congenital cardiac pathologies. NEW & NOTEWORTHY Protein tyrosine phosphatase receptor ζ1 (PTPRZ1) is expressed in fetal but not adult heart and seems to affect heart development. In both mouse and zebrafish animal models, loss of PTPRZ1 results in dilated left ventricle cavity, decreased ejection fraction, and fraction shortening, with no signs of cardiac hypertrophy. PTPRZ1 also seems to be involved in atrioventricular canal specification, outflow tract morphogenesis, and heart angiogenesis. These results suggest that PTPRZ1 plays a role in heart development and support the hypothesis that it may be involved in congenital cardiac pathologies. |
format | Online Article Text |
id | pubmed-8754060 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Physiological Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-87540602022-02-03 Protein tyrosine phosphatase receptor-ζ1 deletion triggers defective heart morphogenesis in mice and zebrafish Katraki-Pavlou, Stamatiki Kastana, Pinelopi Bousis, Dimitris Ntenekou, Despoina Varela, Aimilia Davos, Constantinos H. Nikou, Sophia Papadaki, Eleni Tsigkas, Grigorios Athanasiadis, Emmanouil Herradon, Gonzalo Mikelis, Constantinos M. Beis, Dimitris Papadimitriou, Evangelia Am J Physiol Heart Circ Physiol Research Article Protein tyrosine phosphatase receptor-ζ1 (PTPRZ1) is a transmembrane tyrosine phosphatase receptor highly expressed in embryonic stem cells. In the present work, gene expression analyses of Ptprz1(−/−) and Ptprz1(+/+) mice endothelial cells and hearts pointed to an unidentified role of PTPRZ1 in heart development through the regulation of heart-specific transcription factor genes. Echocardiography analysis in mice identified that both systolic and diastolic functions are affected in Ptprz1(−/−) compared with Ptprz1(+/+) hearts, based on a dilated left ventricular (LV) cavity, decreased ejection fraction and fraction shortening, and increased angiogenesis in Ptprz1(−/−) hearts, with no signs of cardiac hypertrophy. A zebrafish ptprz1(−/−) knockout was also generated and exhibited misregulated expression of developmental cardiac markers, bradycardia, and defective heart morphogenesis characterized by enlarged ventricles and defected contractility. A selective PTPRZ1 tyrosine phosphatase inhibitor affected zebrafish heart development and function in a way like what is observed in the ptprz1(−/−) zebrafish. The same inhibitor had no effect in the function of the adult zebrafish heart, suggesting that PTPRZ1 is not important for the adult heart function, in line with data from the human cell atlas showing very low to negligible PTPRZ1 expression in the adult human heart. However, in line with the animal models, Ptprz1 was expressed in many different cell types in the human fetal heart, such as valvar, fibroblast-like, cardiomyocytes, and endothelial cells. Collectively, these data suggest that PTPRZ1 regulates cardiac morphogenesis in a way that subsequently affects heart function and warrant further studies for the involvement of PTPRZ1 in idiopathic congenital cardiac pathologies. NEW & NOTEWORTHY Protein tyrosine phosphatase receptor ζ1 (PTPRZ1) is expressed in fetal but not adult heart and seems to affect heart development. In both mouse and zebrafish animal models, loss of PTPRZ1 results in dilated left ventricle cavity, decreased ejection fraction, and fraction shortening, with no signs of cardiac hypertrophy. PTPRZ1 also seems to be involved in atrioventricular canal specification, outflow tract morphogenesis, and heart angiogenesis. These results suggest that PTPRZ1 plays a role in heart development and support the hypothesis that it may be involved in congenital cardiac pathologies. American Physiological Society 2022-01-01 2021-11-12 /pmc/articles/PMC8754060/ /pubmed/34767486 http://dx.doi.org/10.1152/ajpheart.00400.2021 Text en Copyright © 2022 The Authors https://creativecommons.org/licenses/by/4.0/Licensed under Creative Commons Attribution CC-BY 4.0 (https://creativecommons.org/licenses/by/4.0/) . Published by the American Physiological Society. |
spellingShingle | Research Article Katraki-Pavlou, Stamatiki Kastana, Pinelopi Bousis, Dimitris Ntenekou, Despoina Varela, Aimilia Davos, Constantinos H. Nikou, Sophia Papadaki, Eleni Tsigkas, Grigorios Athanasiadis, Emmanouil Herradon, Gonzalo Mikelis, Constantinos M. Beis, Dimitris Papadimitriou, Evangelia Protein tyrosine phosphatase receptor-ζ1 deletion triggers defective heart morphogenesis in mice and zebrafish |
title | Protein tyrosine phosphatase receptor-ζ1 deletion triggers defective
heart morphogenesis in mice and zebrafish |
title_full | Protein tyrosine phosphatase receptor-ζ1 deletion triggers defective
heart morphogenesis in mice and zebrafish |
title_fullStr | Protein tyrosine phosphatase receptor-ζ1 deletion triggers defective
heart morphogenesis in mice and zebrafish |
title_full_unstemmed | Protein tyrosine phosphatase receptor-ζ1 deletion triggers defective
heart morphogenesis in mice and zebrafish |
title_short | Protein tyrosine phosphatase receptor-ζ1 deletion triggers defective
heart morphogenesis in mice and zebrafish |
title_sort | protein tyrosine phosphatase receptor-ζ1 deletion triggers defective
heart morphogenesis in mice and zebrafish |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8754060/ https://www.ncbi.nlm.nih.gov/pubmed/34767486 http://dx.doi.org/10.1152/ajpheart.00400.2021 |
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