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机械转导与组蛋白修饰形成的反馈回路的机制及应用

Mechanism and application of feedback loops formed by mechanotransduction and histone modifications.

作者信息

Sun Han, Gao Yafang, Ma Xinyu, Deng Yizhou, Bi Lintao, Li Lisha

机构信息

Department of Hematology and Oncology, China-Japan Union Hospital, Jilin University, Changchun, Jilin 130021, China.

The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, China.

出版信息

Genes Dis. 2023 Aug 2;11(5):101061. doi: 10.1016/j.gendis.2023.06.030. eCollection 2024 Sep.

Abstract

Mechanical stimulation is the key physical factor in cell environment. Mechanotransduction acts as a fundamental regulator of cell behavior, regulating cell proliferation, differentiation, apoptosis, and exhibiting specific signature alterations during the pathological process. As research continues, the role of epigenetic science in mechanotransduction is attracting attention. However, the molecular mechanism of the synergistic effect between mechanotransduction and epigenetics in physiological and pathological processes has not been clarified. We focus on how histone modifications, as important components of epigenetics, are coordinated with multiple signaling pathways to control cell fate and disease progression. Specifically, we propose that histone modifications can form regulatory feedback loops with signaling pathways, that is, histone modifications can not only serve as downstream regulators of signaling pathways for target gene transcription but also provide feedback to regulate signaling pathways. Mechanotransduction and epigenetic changes could be potential markers and therapeutic targets in clinical practice.

摘要

机械刺激是细胞微环境中的关键物理因素。机械转导作为细胞行为的基本调节因子,调控细胞增殖、分化、凋亡,并在病理过程中表现出特定的标志性改变。随着研究的不断深入,表观遗传科学在机械转导中的作用正受到关注。然而,机械转导与表观遗传学在生理和病理过程中协同作用的分子机制尚未阐明。我们关注作为表观遗传学重要组成部分的组蛋白修饰如何与多种信号通路协同作用,以控制细胞命运和疾病进展。具体而言,我们提出组蛋白修饰可与信号通路形成调节反馈环,即组蛋白修饰不仅可作为信号通路的下游调节因子参与靶基因转录,还可提供反馈调节信号通路。机械转导和表观遗传变化可能是临床实践中的潜在标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dfe/11282412/77e235fced7e/gr1.jpg

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