Zhuang Zhao Hui, Zhong Yong, Chen Yuec Han, Zhang Zhi Wei
School of Medicine, Shihezi University, Shihezi 832003, China.
Yi Chuan. 2018 Sep 20;40(9):733-748. doi: 10.16288/j.yczz.18-095.
Krüppel-like factors (KLFs) are a group of transcription factors characterized with three C2H2 zinc fingers at C-terminus. The N-termini of KLFs are highly variable and usually work as a transcriptional regulatory domain. The N-termini of KLFs may also bind to cofactors and change the transcriptional regulation abilities of KLFs. KLFs play important roles in the differentiation and phenotype maintenance of various cells. Additionally, KLFs are involved in the regulation of human physiological processes and in the occurrence and development of the diseases. There are 18 kinds of KLFs identified in human genome. The current reports show that several KLFs regulate the development and functions of the three kinds of muscle tissues in humans and animals. In cardiac muscle, KLF4, KLF10, KLF11 and KLF15 are involved in the negative regulation of cardiac hypertrophy. In addition, KLF6 is involved in the regulation of cardiac fibrosis. KLF13 regulates cardiac muscle development during the embryonic period. In vascular smooth muscle, the post-translated modification of KLF4 is regulated by positive factors of cell proliferation and differentiation and plays important roles in the regulation of the vascular smooth muscle phenotype. In addition, KLF5 promotes vascular smooth muscle proliferation, while KLF8 and KLF15 inhibit vascular smooth muscle proliferation. In skeletal muscle, KLF2, KLF3, KLF4, KLF10 and KLF15 are involved in the regulation of skeletal muscle development. Notably, KLF15 influences the energy metabolism in three kinds of muscle tissues. In conclusion, several KLFs may have the same regulatory mechanism in two or three kinds of muscle tissues. In the same kind of muscle tissue, the synergistic and sequential regulation among KLFs may occur and be important for the development and function regulation of muscle tissues. In this review, we summarize the research progress on the functions and mechanism of KLFs in cardiac muscle, smooth muscle, and skeletal muscle. It also provides references for the further understanding of the functions of KLFs in muscle tissues and reveals the molecular mechanisms of muscle-related diseases.
Krüppel样因子（KLFs）是一类转录因子，其特征是在C末端有三个C2H2锌指结构。KLFs的N末端高度可变，通常作为转录调节域发挥作用。KLFs的N末端也可能与辅因子结合，从而改变KLFs的转录调节能力。KLFs在各种细胞的分化和表型维持中发挥重要作用。此外，KLFs还参与人类生理过程的调节以及疾病的发生和发展。在人类基因组中已鉴定出18种KLFs。目前的报道表明，几种KLFs调节人类和动物三种肌肉组织的发育和功能。在心肌中，KLF4、KLF10、KLF11和KLF15参与心肌肥大的负调控。此外，KLF6参与心肌纤维化的调节。KLF13在胚胎期调节心肌发育。在血管平滑肌中，KLF4的翻译后修饰受细胞增殖和分化的正向因子调控，并在血管平滑肌表型的调节中发挥重要作用。此外，KLF5促进血管平滑肌增殖，而KLF8和KLF15抑制血管平滑肌增殖。在骨骼肌中，KLF2、KLF3、KLF4、KLF10和KLF15参与骨骼肌发育的调节。值得注意的是，KLF15影响三种肌肉组织的能量代谢。总之，几种KLFs可能在两种或三种肌肉组织中具有相同的调节机制。在同一种肌肉组织中，KLFs之间可能发生协同和顺序调节，这对肌肉组织的发育和功能调节很重要。在本综述中，我们总结了KLFs在心肌、平滑肌和骨骼肌中的功能及机制的研究进展。这也为进一步了解KLFs在肌肉组织中的功能提供参考，并揭示肌肉相关疾病的分子机制。
