Liu Renjing, Leslie Kristen L, Martin Kathleen A
Agnes Ginges Laboratory for Diseases of the Aorta, Centre for the Endothelium, Vascular Biology Program, Centenary Institute, Sydney, Australia; Sydney Medical School, University of Sydney, Australia.
Departments of Internal Medicine and Pharmacology, Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Yale University, New Haven, CT 06511, USA.
Biochim Biophys Acta. 2015 Apr;1849(4):448-53. doi: 10.1016/j.bbagrm.2014.06.004. Epub 2014 Jun 15.
Smooth muscle cells (SMC) are the major cell type in blood vessels. Their principal function in the body is to regulate blood flow and pressure through vessel wall contraction and relaxation. Unlike many other mature cell types in the adult body, SMC do not terminally differentiate but retain a remarkable plasticity. They have the unique ability to toggle between a differentiated and quiescent "contractile" state and a highly proliferative and migratory "synthetic" phenotype in response to environmental stresses. While there have been major advances in our understanding of SMC plasticity through the identification of growth factors and signals that can influence the SMC phenotype, how these regulate SMC plasticity remains unknown. To date, several key transcription factors and regulatory cis elements have been identified that play a role in modulating SMC state. The frontier in understanding the molecular mechanisms underlying SMC plasticity has now advanced to the level of epigenetics. This review will summarize the epigenetic regulation of SMC, highlighting the role of histone modification, DNA methylation, and our most recent identification of a DNA demethylation pathway in SMC that is pivotal in the regulation of the SMC phenotypic state. Many disorders are associated with smooth muscle dysfunction, including atherosclerosis, the major underlying cause of stroke and coronary heart disease, as well as transplant vasculopathy, aneurysm, asthma, hypertension, and cancer. An increased understanding of the major regulators of SMC plasticity will lead to the identification of novel target molecules that may, in turn, lead to novel drug discoveries for the treatment of these diseases. This article is part of a Special Issue entitled: Stress as a fundamental theme in cell plasticity.
平滑肌细胞（SMC）是血管中的主要细胞类型。它们在体内的主要功能是通过血管壁的收缩和舒张来调节血流和血压。与成体中的许多其他成熟细胞类型不同，SMC不会终末分化，而是保留了显著的可塑性。它们具有独特的能力，能够根据环境应激在分化且静止的“收缩性”状态与高度增殖和迁移的“合成性”表型之间切换。虽然通过鉴定可影响SMC表型的生长因子和信号，我们对SMC可塑性的理解取得了重大进展，但这些因子如何调节SMC可塑性仍然未知。迄今为止，已经鉴定出几种在调节SMC状态中起作用的关键转录因子和调控顺式元件。目前，在理解SMC可塑性潜在分子机制方面的前沿研究已推进到表观遗传学水平。本综述将总结SMC的表观遗传调控，重点介绍组蛋白修饰、DNA甲基化的作用，以及我们最近在SMC中鉴定出的一条对SMC表型状态调控至关重要的DNA去甲基化途径。许多疾病都与平滑肌功能障碍有关，包括动脉粥样硬化（中风和冠心病的主要潜在病因）、移植血管病、动脉瘤、哮喘、高血压和癌症。对SMC可塑性主要调节因子的深入了解将有助于鉴定新的靶分子，进而可能带来治疗这些疾病的新药发现。本文是名为“应激作为细胞可塑性的基本主题”的特刊的一部分。
