Mechanistic study of transcription factor Sox18 during heart development

IF 2.1 3区医学 Q3 ENDOCRINOLOGY & METABOLISM General and comparative endocrinology Pub Date : 2024-02-17 DOI:10.1016/j.ygcen.2024.114472

Jianxin Liang , Imtiaz Ul Hassan , Man Yee Cheung , Lei Feng , Yi-jyun Lin , Qi Long , Chengdong Wang , Yuyue Ding , Ziqing Wang , Yuan Zhang , Yulong Li , Donghao Guo , Xiaofang Guo , Thomas Chi Bun Wong , Muhammad Kaleem Samma , Zixin Rong , Xufeng Qi , Dongqing Cai , Sai-Ming Ngai , Hui Zhao

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Abstract

Heart development is a delicate and complex process regulated by coordination of various signaling pathways. In this study, we investigated the role of sox18 in heart development by modulating Wnt/β-Catenin signaling pathways. Our spatiotemporal expression analysis revealed that sox18 is mainly expressed in the heart, branchial arch, pharyngeal arch, spinal cord, and intersegmental vessels at the tailbud stage of Xenopus tropicalis embryo. Overexpression of sox18 in the X. tropicalis embryos causes heart edema, while loss-of-function of sox18 can change the signal of developmental heart marker gata4 at different stages, suggesting that sox18 plays an essential role in the development of the heart. Knockdown of SOX18 in human umbilical vein endothelial cells suggests a link between Sox18 and β-CATENIN, a key regulator of the Wnt signaling pathway. Sox18 negatively regulates islet1 and tbx3, the downstream factors of Wnt/β-Catenin signaling, during the linear heart tube formation and the heart looping stage. Taken together, our findings highlight the crucial role of Sox18 in the development of the heart via inhibiting Wnt/β-Catenin signaling.

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心脏发育过程中转录因子 Sox18 的机制研究

心脏发育是一个微妙而复杂的过程，受各种信号通路的协调调控。本研究探讨了sox18通过调节Wnt/β-Catenin信号通路在心脏发育中的作用。我们的时空表达分析发现，在热带爪蟾胚胎的尾芽期，sox18主要在心脏、支弓、咽弓、脊髓和节间血管中表达。在X. tropicalis胚胎中过表达sox18会导致心脏水肿，而sox18功能缺失会改变不同阶段心脏发育标志物gata4的信号，这表明sox18在心脏发育中起着至关重要的作用。敲除人脐静脉内皮细胞中的SOX18表明，Sox18与Wnt信号通路的关键调节因子β-CATENIN之间存在联系。在线性心管形成和心脏环形阶段，Sox18 负向调节 Wnt/β-Catenin 信号转导的下游因子 islet1 和 tbx3。综上所述，我们的研究结果凸显了 Sox18 通过抑制 Wnt/β-Catenin 信号在心脏发育过程中的关键作用。

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来源期刊

General and comparative endocrinology 医学-内分泌学与代谢

CiteScore

5.60

自引率

7.40%

发文量

120

审稿时长

2 months

期刊介绍： General and Comparative Endocrinology publishes articles concerned with the many complexities of vertebrate and invertebrate endocrine systems at the sub-molecular, molecular, cellular and organismal levels of analysis.