Kruppel-like Factors (KLFs) in muscle biology

Abstract

The Kruppel-like Factor (KLF) family of zinc-finger transcription factors are critical regulators of cell differentiation, phenotypic modulation and physiologic function. An emerging body of evidence implicates an important role for these factors in cardiovascular biology, however, the role of KLFs in muscle biology is only beginning to be understood. This article reviews the published data describing the role of KLFs in the heart, smooth muscle, and skeletal muscle and highlights the importance of these factors in cardiovascular development, physiology and disease pathobiology.

Figure 1

Kruppel-Like Factors are Important Regulators of Muscle Biology in the Cardiovascular System. (A) KLF15 is expressed in cardiomyocytes, SMC and skeletal muscle [27, 40]. KLF15 (+/−) mice were generated by targeting the native mouse KLF15 gene with a lacZ cassette containing a nuclear localization signal. Histologic sections from KLF15 (+/+) vs. (+/−) tissues are shown. KLF15 (+/−) tissues are shown both with and without eosin counterstaining. (Adapted with permission from PNAS and JBC) (B) KLF5 (+/−) mice have reduced neointimal formation in response to vascular injury (top) and reduced perivascular fibrosis in response to angiotensin II infusion (bottom) [28]. (Adapted with permission from Nature Medicine). (C) KLF15 (−/−) develop eccentric hypertrophy, severe LV dysfunction, and eccentric myocyte enlargement with pressure overload [27]. (Adapted with permission from PNAS). (D) KLF13 knockdown in Xenopus embryos causes atrial septal abnormalities and defects in ventricular trabeculation [37]. (Adapted with permission from EMBO Journal)