[Research progress on the roles of Krüppel-like factors in muscle tissues]

Abstract

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.