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Protein tyrosine phosphatase receptor zeta 1 deletion triggers defective heart morphogenesis in mice and zebrafish
American Journal of Physiology-Heart and Circulatory Physiology ( IF 4.1 ) Pub Date : 2021-11-12 , DOI: 10.1152/ajpheart.00400.2021
Stamatiki Katraki-Pavlou 1, 2 , Pinelopi Kastana 1 , Dimitris Bousis 1 , Despoina Ntenekou 1 , Aimilia Varela 3 , Constantinos H Davos 3 , Sophia Nikou 4 , Eleni Papadaki 4 , Grigorios Tsigkas 5 , Emmanouil Athanasiadis 6 , Gonzalo Herradon 7 , Constantinos M Mikelis 1, 8 , Dimitris Beis 2 , Evangelia Papadimitriou 1
Affiliation  

Protein tyrosine phosphatase receptor zeta 1 (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 regulation of heart-specific transcription factor genes. Echocardiography analysis in mice identified that both systolic and diastolic functions are affected in Ptprz1-/- compared to Ptprz1+/+ hearts, based on a dilated 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 exhibits mis-regulated 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.

中文翻译:

蛋白酪氨酸磷酸酶受体zeta 1缺失引发小鼠和斑马鱼心脏形态发生缺陷

蛋白酪氨酸磷酸酶受体 zeta 1 (PTPRZ1) 是一种在胚胎干细胞中高表达的跨膜酪氨酸磷酸酶受体。在目前的工作中,Ptprz1 -/-和 Ptprz1 +/+小鼠内皮细胞和心脏的基因表达分析指出,PTPRZ1 通过调节心脏特异性转录因子基因在心脏发育中的作用尚未确定。小鼠超声心动图分析发现,与 Ptprz1 +/+心脏相比, Ptprz1 -/-心脏的收缩和舒张功能均受到影响,基于扩张的 LV 腔、射血分数降低和分数缩短,以及 Ptprz1 -/-心脏血管生成增加,没有心脏肥大的迹象。斑马鱼 ptprz1-/-也产生了基因敲除,并表现出发育性心脏标志物、心动过缓和以心室扩大和收缩力缺陷为特征的有缺陷的心脏形态发生的错误调节表达。选择性 PTPRZ1 酪氨酸磷酸酶抑制剂影响斑马鱼心脏发育和功能的方式类似于在 ptprz1 中观察到的-/-斑马鱼。相同的抑制剂对成年斑马鱼心脏的功能没有影响,这表明 PTPRZ1 对成年心脏功能并不重要,这与来自人类细胞图谱的数据一致,显示成年人类心脏中 PTPRZ1 的表达非常低甚至可以忽略不计。然而,与动物模型一致,Ptprz1 在人类胎儿心脏的许多不同细胞类型中表达,例如瓣膜细胞、成纤维细胞样细胞、心肌细胞和内皮细胞。总的来说,这些数据表明 PTPRZ1 以随后影响心脏功能的方式调节心脏形态发生,并需要进一步研究 PTPRZ1 参与特发性先天性心脏病。
更新日期:2021-11-13
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