Department of Medicine-Cardiology, University of California San Diego,Gilman Drive, Mail Code, La Jolla, California, United States of America.
Department of Cardiology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, China.
PLoS Genet. 2020 Apr 6;16(4):e1008730. doi: 10.1371/journal.pgen.1008730. eCollection 2020 Apr.
O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) is the only enzyme catalyzing O-GlcNAcylation. Although it has been shown that OGT plays an essential role in maintaining postnatal heart function, its role in heart development remains unknown. Here we showed that loss of OGT in early fetal cardiomyocytes led to multiple heart developmental defects including hypertrabeculation, biventricular dilation, atrial septal defects, ventricular septal defects, and defects in coronary vessel development. In addition, RNA sequencing revealed that Angiopoietin-1, required within cardiomyocytes for both myocardial and coronary vessel development, was dramatically downregulated in cardiomyocyte-specific OGT knockout mouse hearts. In conclusion, our data demonstrated that OGT plays an essential role in regulating heart development through activating expression of cardiomyocyte Angiopoietin-1.
O-连接 N-乙酰葡萄糖胺（GlcNAc）转移酶（OGT）是唯一催化 O-GlcNAcylation 的酶。虽然已经表明 OGT 在维持出生后心脏功能方面起着至关重要的作用，但它在心脏发育中的作用尚不清楚。在这里，我们发现早期胎儿心肌细胞中 OGT 的缺失导致多种心脏发育缺陷，包括心壁过度生长、双心室扩张、房间隔缺损、室间隔缺损以及冠状血管发育缺陷。此外，RNA 测序显示，血管生成素 1（Angiopoietin-1）是心肌和冠状血管发育所必需的，在心肌细胞特异性 OGT 敲除小鼠心脏中其表达显著下调。总之，我们的数据表明，OGT 通过激活心肌细胞血管生成素 1 的表达，在调节心脏发育中发挥重要作用。
