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Krüppel 样因子与血管壁稳态。

Krüppel-like factors and vascular wall homeostasis.

机构信息

Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, USA.

出版信息

J Mol Cell Biol. 2017 Oct 1;9(5):352-363. doi: 10.1093/jmcb/mjx037.

Abstract

Cardiovascular diseases (CVDs) are major causes of death worldwide. Identification of promising targets for prevention and treatment of CVDs is paramount in the cardiovascular field. Numerous transcription factors regulate cellular function through modulation of specific genes and thereby are involved in the physiological and pathophysiological processes of CVDs. Although Krüppel-like factors (KLFs) have a similar protein structure with a conserved zinc finger domain, they possess distinct tissue and cell distribution patterns as well as biological functions. In the vascular system, KLF activities are regulated at both transcriptional and posttranscriptional levels. Growing in vitro, in vivo, and genetic epidemiology studies suggest that specific KLFs play important roles in vascular wall biology, which further affect vascular diseases. KLFs regulate various functional aspects such as cell growth, differentiation, activation, and development through controlling a whole cluster of functionally related genes and modulating various signaling pathways in response to pathological conditions. Therapeutic targeting of selective KLF family members may be desirable to achieve distinct treatment effects in the context of various vascular diseases. Further elucidation of the association of KLFs with human CVDs, their underlying molecular mechanisms, and precise protein structure studies will be essential to define KLFs as promising targets for therapeutic interventions in CVDs.

摘要

心血管疾病 (CVDs) 是全球主要的死亡原因。在心血管领域,确定有前途的 CVDs 预防和治疗靶点至关重要。许多转录因子通过调节特定基因来调节细胞功能,从而参与 CVDs 的生理和病理生理过程。虽然 Krüppel 样因子 (KLFs) 具有相似的蛋白质结构,具有保守的锌指结构域,但它们具有不同的组织和细胞分布模式以及生物学功能。在血管系统中,KLF 的活性在转录和转录后水平受到调节。越来越多的体外、体内和遗传流行病学研究表明,特定的 KLF 在血管壁生物学中发挥重要作用,进一步影响血管疾病。KLF 通过控制一整组功能相关基因并调节各种信号通路来调节各种功能方面,例如细胞生长、分化、激活和发育,以响应病理条件。针对选择性 KLF 家族成员进行治疗靶向可能是理想的,以在各种血管疾病的背景下实现不同的治疗效果。进一步阐明 KLFs 与人类 CVDs 的关联、其潜在的分子机制以及精确的蛋白质结构研究对于将 KLFs 定义为 CVDs 治疗干预的有前途的靶点至关重要。

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