作为治疗主动脉疾病潜在药物靶点的转化生长因子 β 信号通路

Zijie Liu, Tianyu Song, Liping Xie
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综述转化生长因子β信号通路是治疗主动脉疾病的潜在药物靶点刘子杰1,2, 宋天宇3, 谢丽萍1,2,3, *1 心血管疾病靶向干预重点实验室,心血管疾病转化医学协同创新中心、南京医科大学基础医学院,南京,211166 ‍ 南京医科大学心脑血管病医学重点实验室,南京,211166* 通讯地址:南京医科大学基础医学院:lipingxie@njmu.edu.cn 接收:摘要:转化生长因子β(TGF-‍β)信号通路对维持主动脉结构平衡和促进主动脉发育至关重要。该途径包括依赖 SMAD 的典型途径和不依赖 SMAD 的非典型信号途径。遗传性胸主动脉瘤和夹层与 TGF-‍β 典范信号相关基因的遗传改变高度相关。然而,根据疾病的不同阶段,TGF-‍β 信号通路既可产生抑制作用,也可产生加重作用,这使得其在主动脉疾病中的作用变得复杂,有时甚至相互矛盾。本综述旨在阐明 TGF-‍β 信号通路在最常见的主动脉疾病(即急性主动脉综合征和主动脉瘤)中的生物学机制,并评估 TGF-β 靶向疗法在主动脉疾病中的潜在临床应用。
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Transforming Growth Factor β Signaling Pathway as a Potential Drug Target in Treating Aortic Diseases
Review Transforming Growth Factor β Signaling Pathway as a Potential Drug Target in Treating Aortic Diseases Zijie Liu 1,2, Tianyu Song 3, and Liping Xie 1,2,3, * 1  Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing 211166, China 2  School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, China 3  ‍Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Nanjing Medical University, Nanjing 211166, China * Correspondence: lipingxie@njmu.edu.cn     Received: 16 October 2023 Accepted: 20 November 2023 Published: 6 March 2024   Abstract: The transforming growth factor β (TGF-‍β) signaling pathway is crucial for preserving the structural homeostasis of the aorta and promoting aortic development. This pathway encompasses both SMAD-dependent canonical pathway and SMAD-independent non-canonical signaling pathway. Heritable thoracic aortic aneurysms and dissection are highly correlated with genetic alterations in TGF-‍β canonical signaling-related genes. However, depending on the stage of the disease, the TGF-‍β signaling pathway can have either inhibitory or aggravation effects, making its roles in aortic disease complex and occasionally contradictory. This review aims to elucidate the biological mechanisms underlying the TGF-‍β signaling pathway in the most common aortic diseases, namely acute aortic syndromes and aortic aneurysms, and to evaluate the potential clinical application of TGF-β-targeting therapies in aortic diseases.
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