LncRNA PSR Regulates Vascular Remodeling Through Encoding a Novel Protein Arteridin.
LncRNA PSR Regulates Vascular Remodeling Through Encoding a Novel Protein Arteridin.
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LncRNA PSR 通过编码新型蛋白质 Arteridin 调节血管重塑
DOI：
10.1161/circresaha.122.321080
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发表时间：
2022-10-14
影响因子：
20.1
通讯作者：
Zeng, Chunyu
中科院分区：
文献类型：
--
作者：
Yu, Junyi;Wang, Wei;Yang, Jining;Zhang, Ye;Gong, Xue;Luo, Hao;Cao, Nian;Xu, Zaicheng;Tian, Miao;Yang, Peili;Mei, Qiao;Chen, Zhi;Li, Zhuxin;Li, Chuanwei;Duan, Xudong;Lyu, Qing Rex;Gao, Chen;Zhang, Bing;Wang, Yibin;Wu, Gengze;Zeng, Chunyu
血管平滑肌细胞（VSMC）表型从收缩表型转变为增殖表型是各种心血管疾病的病理标志。最近，长非编码 RNA (lncRNA) 的一个子集被鉴定可产生功能性多肽。然而，lncRNA在VSMC表型转换中的功能影响和调节机制仍有待充分阐明。阐明富含 VSMC 的 lncRNA 及其编码肽在 VSMC 表型转换和血管重塑中的生物学功能和机制。我们鉴定了一种富含 VSMC 的转录物，该转录物由以前未表征的基因编码，我们称之为表型转换调节器（PSR），该基因在血管重塑过程中显着上调。尽管 PSR 被注释为 lncRNA，但我们证明 lncPSR 还编码一种蛋白质，我们将其命名为 Arteridin。在 VSMC 中，Arteridin 和 lncPSR 对于诱导表型转换都是必要且充分的。从机制上讲，Arteridin 和 lncPSR 通过直接与转录因子 YBX1 相互作用并调节其核易位和染色质靶向来调节下游基因。有趣的是，Arteridin 也强烈诱导 PSR 转录。更重要的是，PSR基因或Arteridin蛋白的缺失显着减弱了颈动脉损伤引起的血管重塑。此外，使用腺相关病毒（AAV）对lncPSR进行VSMC特异性抑制可减弱血管紧张素II（Ang II）诱导的高血压血管重塑。 PSR 是一种富含 VSMC 的基因，其编码的转录本 (lncPSR) 和蛋白质 (Arteridin) 通过共享的相互作用伙伴 YBX1 协调调节转录重编程。这是血管重塑过程中 VSMC 表型转换中以前未表征的调节回路，lncPSR/Arteridin 作为治疗 VSMC 表型转换相关血管重塑的潜在治疗靶点。
Vascular smooth muscle cells (VSMCs) phenotype switch from contractile to proliferative phenotype is a pathological hallmark in various cardiovascular diseases. Recently, a subset of long non-coding RNAs (lncRNAs) was identified to produce functional polypeptides. However, the functional impact and regulatory mechanisms of lncRNAs in VSMCs phenotype switching remain to be fully elucidated. To illustrate the biological function and mechanism of a VSMC-enriched lncRNA and its encoded peptide in VSMC phenotype switching and vascular remodeling. We identified a VSMC-enriched transcript encoded by a previously uncharacterized gene, we called Phenotype-Switching-Regulator (PSR), which was markedly up-regulated during vascular remodeling. Although PSR was annotated as a lncRNA, we demonstrated that the lncPSR also encoded a protein, which we named Arteridin. In VSMCs, both Arteridin and lncPSR were necessary and sufficient to induce phenotype switching. Mechanistically, Arteridin and lncPSR regulate downstream genes by directly interacting with a transcription factor YBX1 and modulating its nuclear translocation and chromatin targeting. Intriguingly, the PSR transcription was also robustly induced by Arteridin. More importantly, the loss of PSR gene or Arteridin protein significantly attenuated the vascular remodeling induced by carotid arterial injury. In addition, VSMC-specific inhibition of lncPSR using adeno-associated virus (AAV) attenuated angiotensin II (Ang II)-induced hypertensive vascular remodeling. PSR is a VSMC-enriched gene, and its encoded transcript (lncPSR) and protein (Arteridin) coordinately regulate transcriptional reprogramming through a shared interacting partner, YBX1. This is a previously uncharacterized regulatory circuit in VSMC phenotype switching during vascular remodeling, with lncPSR/Arteridin as potential therapeutic targets for the treatment of VSMC phenotype switching related vascular remodeling.
影响因子：
3.7
作者：
Bakker EN;Groma G;Spijkers LJ;de Vos J;van Weert A;van Veen H;Everts V;Arribas SM;VanBavel E
通讯作者：
VanBavel E