苯肾上腺素诱导KLF5和hhLIM协同激活心肌肥大标志基因表达.pdfVIP

英 文 摘 要 PE-induced KLF5 and hhLIM cooperatively activate expression of cardiac hypertrophy marker gene ABSTRACT Objective: Cardiac hypertrophy is one of adaptive responses of the heart to a variety of pathological stimuli, including hypertension, myocardial infarction, congenital heart disease, heart valvula disease, and perturbations in sarcomeric function, and is the main reason of the refractory heart failure. But the mechanism of cardiac hypertrophy is still not very clear. LIM proteins contain one, two or multiple cysteine-rich zinc-finger motifs and have been discovered to play important roles in a variety of fundamental biological processes including cytoskeleton organization, cell lineage specification and organ development. hhLIM, also named hLIM3 (GenBank AF121260), was cloned by three-element subtraction method from the embryo heart cDNA library. It is one of the members of LIM family since it has the typical LIM domain. Our previous study confirmed that hhLIM can shuttle between the nucleus and the cytoplasm. In differentiated cells, hhLIM mainly distributes in cytoplasm and enhances the stability of the actin cytoskeleton and promotes actin bundling, and then maintains the contractile function of myocardium. In response to stimuli inducing hypertrophy, hhLIM protein shuttled from cytoplasm to nucleus. In the nucleus, hhLIM interacted with Nkx2.5 and synergistically activated the expression of BNP and α-actin. Krüppel-like factors (KLFs) belong to the transcription factor family containing zinc-finger structures, mainly involved in regulating cell growth, differentiation, proliferation and apoptosis. As one of the members of this family,