PARP1 regulates VSMC phenotypic switch and neointima via Myocardin

We applied the transcriptome profiling (RNA-seq) for high-throughput profiling of genes changes in VSMC dedifferentiation. Rat primary VSMCs were divided into 3 groups, control, PDGF-BB, PDGF-BB+PJ34,and mRNA sequence were performed. We found that PDGF-BB could upregualted the genes involved in cell proliferation and migration, and downregulated the VSMC contractile genes, all of which could be reversed by PARP inhibitor PJ34. Then we knockdowned the co-factor Myocardin in VSMCs, and found the above effects of PJ34 were nearly abolished.Our study first provided the transcription changes by RNA-seq in VSMC dedifferentiation, and demonstrated the key roles of PARP1 and the PARylation process in VSMC phenotypic switch.本研究采用转录组测序（RNA-seq）对血管平滑肌细胞（Vascular Smooth Muscle Cell, VSMC）去分化过程中的基因表达变化开展高通量分析。将大鼠原代血管平滑肌细胞分为三组：对照组、PDGF-BB处理组、PDGF-BB与PJ34联合处理组，并进行mRNA测序。结果显示，PDGF-BB可上调参与细胞增殖与迁移的基因，同时下调血管平滑肌细胞收缩表型相关基因，上述效应均可被聚ADP核糖聚合酶（PARP）抑制剂PJ34逆转。随后，我们在血管平滑肌细胞中敲降辅因子Myocardin，发现PJ34的上述调控作用几乎被完全阻断。本研究首次通过RNA-seq获取了血管平滑肌细胞去分化过程中的转录组变化，并证实了PARP1及其聚ADP核糖基化（PARylation）过程在血管平滑肌细胞表型转化中的关键调控作用。