Genome-wide analysis of gene expression changes in miR-214 KO mouse hearts and skeletal muscle

Early reperfusion of ischemic cardiac tissue remains the most effective intervention for improving clinical outcome following myocardial infarction. However, abrupt increases in intracellular Ca2+ during myocardial reperfusion cause cardiomyocyte death and consequent loss of cardiac function, referred to as ischemia/reperfusion (IR) injury. Cardiac IR is accompanied by dynamic changes in expression of microRNAs (miRNAs), which inhibit specific mRNA targets. miR-214 is up-regulated during ischemic injury and heart failure in mice and humans, but its potential role in these processes is unknown. We show that genetic deletion of miR-214 in mice causes loss of cardiac contractility, increased apoptosis, and excessive fibrosis in response to IR injury. The microarray contains 6 samples, each containing cDNA pooled from 3 mice per group. There are no replicates. The array was designed to make 3 different pairwise comparisons between the following: P14 WT and miR-214 KO hearts; adult WT and miR-214 KO skeletal muscle; adult WT and miR-214 KO hearts缺血心肌组织的早期再灌注仍是改善心肌梗死患者临床结局的最有效干预手段。然而，心肌再灌注过程中细胞内钙离子的骤然升高会引发心肌细胞死亡，进而导致心功能丧失，这一过程被称为缺血再灌注（IR）损伤。心脏缺血再灌注损伤伴随微小RNA（microRNAs, miRNAs）表达的动态变化，此类RNA可抑制特定信使RNA（mRNA）靶标。miR-214在小鼠与人类的缺血性损伤及心力衰竭进程中表达上调，但其在上述病理过程中的潜在作用仍未明确。本研究证实，小鼠体内miR-214的基因敲除会使其心脏在遭受IR损伤时出现心肌收缩功能丧失、细胞凋亡水平升高以及过度纤维化的表型。本次实验使用的基因微阵列（microarray）共包含6个样本，每组取3只小鼠的互补DNA（complementary DNA, cDNA）混合制备样本，且未设置生物学重复。该芯片设计了3组不同的两两比较实验，分别为：出生后第14天（P14）的野生型（wild type, WT）与miR-214敲除（knockout, KO）小鼠心脏；成年野生型与miR-214敲除小鼠的骨骼肌；成年野生型与miR-214敲除小鼠的心脏。