FTO suppresses cardiac fibrosis after myocardial infarction via m6A-mediated epigenetic modification [MeRIP-seq]

Cardiac fibrosis is common in cardiovascular diseases. N6-methyladenosine (m6A) is one of the most common modifications in eukaryotic mRNAs. Previous research has suggested that m6A modification is vital in cardiovascular diseases. The underlying targets of FTO were selected through transcriptome sequencing (RNA-seq) combined with methylated RNA immunoprecipitation sequencing (MeRIP-seq). According to MeRIP-seq and RNA-seq, FTO inhibited collagen synthesis in CFs. Neonatal rat cardiac fibroblasts (NRCFs) were collected from healthy Sprague-Dawley rats within 3 days post-birth. NRCFs were transfected with the plasmid of FTO and Vector and performed comparative m6A expression profiling between FTO and Vector groups.

心肌纤维化（Cardiac fibrosis）在心血管疾病中十分常见。N6-甲基腺嘌呤（N6-methyladenosine, m6A）是真核生物mRNA中最常见的修饰类型之一。既往研究表明，m6A修饰在心血管疾病中发挥至关重要的作用。本研究通过转录组测序（transcriptome sequencing, RNA-seq）联合甲基化RNA免疫沉淀测序（methylated RNA immunoprecipitation sequencing, MeRIP-seq）筛选得到FTO的潜在作用靶点。基于MeRIP-seq与RNA-seq的分析结果，FTO可抑制心肌成纤维细胞（cardiac fibroblasts, CFs）的胶原蛋白合成。实验所需的新生大鼠心肌成纤维细胞（Neonatal rat cardiac fibroblasts, NRCFs）采集自出生3天内的健康斯普拉格-道利（Sprague-Dawley, SD）大鼠。将NRCFs分别转染FTO质粒与空载体（Vector），随后对FTO组与空载体组开展m6A表达谱的对比分析。