Transcriptional Programming in Arteriosclerotic Disease: A Multifaceted Function of the Runx2 (Runt-Related Transcription Factor 2).
Transcriptional Programming in Arteriosclerotic Disease: A Multifaceted Function of the Runx2 (Runt-Related Transcription Factor 2).
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DOI：
10.1161/atvbaha.120.313791
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Wu H
中科院分区：
文献类型：
--
作者：
Chen Y;Zhao X;Wu H
尽管在预防和治疗动脉硬化方面取得了成功的治疗策略，但心血管并发症仍然是世界范围内的一个重大临床和社会问题。血管钙化增加会增加动脉僵硬，加速心血管疾病的发病率和死亡率。Run-Related转录因子2(Runx2)是一种重要的成骨转录因子，在心血管系统中表达上调，是心血管病理过程中不良细胞事件的重要调节因子。本文讨论了对Runx2的表达和功能至关重要的调控机制，并着重介绍了多种翻译后修饰(PTM)在调节Runx2的稳定性、细胞定位和成骨转录活性中的动态和复杂的相互作用，包括磷酸化、乙酰化、泛素化和O-GlcN酰化。综述了循环和局部微环境因素激活的一系列信号通路如何上调血管细胞中的Runx2，并促进Runx2介导的血管平滑肌细胞成骨转分化和炎性细胞因子的表达，从而加速巨噬细胞的浸润和血管破骨细胞的形成。此外，还讨论了Runx2上调在促进VSMC表型转换中的新作用，以及O-GlcN酰化和依赖Runx2抑制SMC特异性基因表达的蛋白质调节。进一步探索这一关键的成骨转录因子的调控及其在血管系统中的新视角，将为VSMC表型转换、重编程和促进动脉硬化发病机制的血管炎症的转录调控提供新的见解。
Despite successful therapeutic strategies in the prevention and treatment of arteriosclerosis, the cardiovascular complications remain a major clinical and societal issue worldwide. Increased vascular calcification promotes arterial stiffness and accelerates cardiovascular morbidity and mortality. Upregulation of the Runt-related transcription factor 2 (Runx2), an essential osteogenic transcription factor for bone formation, in the cardiovascular system has emerged as an important regulator for adverse cellular events that drive cardiovascular pathology. This review discusses the regulatory mechanisms that are critical for Runx2 expression and function, and highlights the dynamic and complex cross-talks of a wide variety of posttranslational modifications (PTMs), including phosphorylation, acetylation, ubiquitination, and O-GlcNAcylation, in regulating Runx2 stability, cellular localization and osteogenic transcriptional activity. How the activation of an array of signaling cascades by circulating and local microenvironmental factors upregulates Runx2 in vascular cells and promotes Runx2-mediated osteogenic trans-differentiation of vascular smooth muscle cells (VSMC) and expression of inflammatory cytokines that accelerate macrophage infiltration and vascular osteoclast formation is summarized. Furthermore, the increasing appreciation of a new role of Runx2 upregulation in promoting VSMC phenotypic switch, and protein modulation by O-GlcNAcylation and Runx2-dependent repression of SMC-specific gene expression are discussed. Further exploring the regulation of this key osteogenic transcription factor and its new perspectives in the vasculature will provide novel insights into the transcriptional regulation of VSMC phenotype switch, reprograming and vascular inflammation that promote the pathogenesis of arteriosclerosis.
影响因子：
1.8
作者：
Robertson AJ;Larroux C;Degnan BM;Coffman JA
通讯作者：
Coffman JA