Soluble RARRES1 induces podocyte apoptosis to promote glomerular disease progression

We try to explore the effect of RARRES1 on human podocyte, so we performed RARRES1 overexpression and knockdown experiments. cell mRNA profiles of human human podocyte cell lines transfected with RARRES1 overexpression vectors orcontrol vectors; and cells transfected with RARRES1 shRNA lentivirus or scramble shRNA lentivirus and stimulated with TNFa (10ng/ml) or without TNFa for 24 hours were generated by deep sequencing, in triplicate, using Illumina GAIIx. The sequence reads that passed quality filters were analyzed at the transcript. We found that most differentially expressed genes (DEGs) are enriched with cell migration and apoptosis-related pathways, also DEGs stimulated by TNFa but suppressed by RARRES1 knockdown, were also enriched with cell cycle-related pathways.These data suggest that RARRES1 plays a key role in the regulation of cell cycle and apoptosis, consistent with its role as a tumor suppressor gene. Overall design: Examination of the effect of RARRES1 on human podocyte

本研究旨在探究视黄酸受体应答蛋白1（RARRES1）对人足细胞的调控作用，故而开展了RARRES1过表达与基因敲低实验。本研究采用Illumina GAIIx平台，通过深度测序技术对三组生物学重复样本的转录组mRNA谱进行分析，所涉样本包括：转染RARRES1过表达载体或空载对照载体的人足细胞系；转染RARRES1短发夹RNA（shRNA）慢病毒或阴性对照shRNA慢病毒，并经10ng/ml肿瘤坏死因子α（TNF-α）刺激或未刺激培养24小时的人足细胞。对通过质量过滤的测序读段开展转录本水平数据分析。研究结果显示，绝大多数差异表达基因（DEGs）显著富集于细胞迁移与细胞凋亡相关通路；此外，经TNF-α诱导但可被RARRES1敲低抑制的差异表达基因，亦显著富集于细胞周期相关通路。上述数据表明，RARRES1在细胞周期与细胞凋亡的调控中发挥关键作用，这与其作为肿瘤抑制基因的功能属性一致。整体实验设计：探究RARRES1对人足细胞的调控作用。