KLF4 和 SIAT7A 的相互作用加速了 Ang II 诱导的心肌肥大。

IF 5.3
Qiying Yao, Xinrui Hu, Tiantian Bian, Qing Zhang, Zhao Xue, Yuesheng Lv, Shupeng Ren, Yue Chen, Dongmei Zhang, Liang Chen
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引用次数: 0

摘要

由 Sialyltransferase 7A (SIAT7A) 催化的 Sialylation 在心脏肥大的发展过程中发挥着作用。然而,SIAT7A 上游的调控机制仍未得到充分阐明。之前的研究表明,KLF4 通过与缺血心肌中的 SIAT7A 基因启动子区域结合来激活该基因。然而,KLF4 是否可能参与调节 Ang II 诱导的肥厚型心肌细胞中 SIAT7A 的表达仍不确定。本研究试图深化 KLF4 和 SIAT7A 在 Ang II 诱导的心肌肥厚进展过程中相互作用的内在机制。结果显示,在本质性高血压患者的肥厚心肌和受 Ang II 刺激的肥厚心肌细胞中,SIAT7A 和 KLF4 的水平同时升高。体外实验显示,降低 KLF4 水平会导致 SIAT7A 合成和 Sialyl-Tn 抗原表达减少,从而抑制 Ang II 诱导的心肌细胞肥大。耐人寻味的是,降低 SIAT7A 水平也会导致 KLF4 表达减少,抑制心肌细胞肥大。与此相一致,在体内和体外实验中,提高 SIAT7A 的水平会增加 KLF4 的表达并加剧心肌细胞肥大。此外,时间进程分析表明,KLF4 的表达先于 SIAT7A 的表达。荧光素酶报告实验进一步证实,调节 SIAT7A 的水平会直接影响 KLF4 在心肌细胞中的转录活性。总之,在接受 Ang II 处理的心肌细胞中,KLF4 的表达上调,随后诱导 SIAT7A 的表达。SIAT7A 水平的升高反过来又增强了 KLF4 的转录。这些发现表明,KLF4 和 SIAT7A-Sialyl-Tn 之间存在正反馈循环,最终促进了 Ang II 诱导的心肌肥大。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Role of KLF4 and SIAT7A interaction accelerates myocardial hypertrophy induced by Ang II

Role of KLF4 and SIAT7A interaction accelerates myocardial hypertrophy induced by Ang II

Sialylation catalysed by sialyltransferase 7A (SIAT7A) plays a role in the development of cardiac hypertrophy. However, the regulatory mechanisms upstream of SIAT7A in this context remain poorly elucidated. Previous study demonstrated that KLF4 activates the SIAT7A gene in ischemic myocardium by binding to its promoter region. Nevertheless, the potential involvement of KLF4 in regulating SIAT7A expression in Ang II-induced hypertrophic cardiomyocytes remains uncertain. This study seeks to deepen the underlying mechanisms of the KLF4 and SIAT7A interaction in the progression of Ang II-induced cardiac hypertrophy. The results showed a concurrent increase in SIAT7A and KLF4 levels in hypertrophic myocardium of essential hypertension patients and in hypertrophic cardiomyocytes stimulated by Ang II. In vitro experiments revealed that reducing KLF4 levels led to a decrease in both SIAT7A synthesis and Sialyl-Tn antigen expression, consequently inhibiting Ang II-induced cardiomyocyte hypertrophy. Intriguingly, reducing SIAT7A levels also resulted in decreased KLF4 expression and suppression cardiomyocyte hypertrophy. Consistent with this, elevating SIAT7A levels increased KLF4 expression and exacerbated cardiomyocyte hypertrophy in both in vivo and in vitro experiments. Additionally, a time-course analysis indicated that KLF4 expression preceded that of SIAT7A. Luciferase reporter assays further confirmed that modulating SIAT7A levels directly influenced the transcriptional activity of KLF4 in cardiomyocytes. In summary, KLF4 expression is upregulated in cardiomyocytes treated with Ang II, which subsequently induces the expression of SIAT7A. The elevated levels of SIAT7A, in turn, enhance the transcription of KLF4. These findings suggest a positive feedback loop between KLF4 and SIAT7A-Sialyl-Tn, ultimately promoting Ang II-induced cardiac hypertrophy.

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CiteScore
11.50
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期刊介绍: The Journal of Cellular and Molecular Medicine serves as a bridge between physiology and cellular medicine, as well as molecular biology and molecular therapeutics. With a 20-year history, the journal adopts an interdisciplinary approach to showcase innovative discoveries. It publishes research aimed at advancing the collective understanding of the cellular and molecular mechanisms underlying diseases. The journal emphasizes translational studies that translate this knowledge into therapeutic strategies. Being fully open access, the journal is accessible to all readers.
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