Krüppel样因子(Krüppel-like factors, KLFs)是一类C-末端含有3个C₂H₂锌指结构的转录因子,N-末端为转录调控结构域,能够结合多种特异蛋白质,介导转录调控。目前在人体基因组中共发现18种KLFs,它们在多种类型人类细胞的分化、表型维持和生理功能调控中发挥重要作用。多个KLFs参与了对人和动物的心肌、平滑肌和骨骼肌的发育和功能的调控。在心肌中,KLF4、KLF10、KLF11和KLF15参与心肌肥大的负调控,KLF6参与调控心脏纤维化,KLF13调控胚胎时期的心肌发育。在血管平滑肌中,KLF4受促增殖或促分化因子调控,介导调控血管平滑肌表型转换;KLF5促进血管平滑肌增殖,KLF8和KLF15抑制血管平滑肌增殖。在骨骼肌中,KLF2、KLF3、KLF4、KLF10和KLF15调控骨骼肌发育,此外,KLF15是肌肉组织能量代谢的调节因子。本文综述了KLFs在心肌、平滑肌和骨骼肌中的功能研究进展,为进一步揭示KLFs在肌肉组织中的作用和肌肉相关疾病的分子机制提供参考。

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.