Department of cardiology, Shunde hospital, Southern Medical University (The first people's hospital of Shunde, Foshan), Guangdong, China.
Second Medical College of Southern Medical University, Guangzhou, China.
Int J Med Sci. 2020 Mar 26;17(7):946-952. doi: 10.7150/ijms.42586. eCollection 2020.
The underlying mechanisms that mediate the effects of vitamin C on endothelial cell aging are widely unknown. To investigate whether Piwi-interacting RNAs (piRNAs) are involved in this process, an endothelial aging model was induced using HO in human umbilical vein endothelial cells (HUVECs) and then treated with vitamin C (VC). Untreated HUVECs without HO exposure were used to serve as the negative control group. Cell cycle, cell viability, and aging-associated protein expression were assessed, and RNA sequencing was performed to reveal the piRNA profile. Functional and regulatory networks of the different piRNA target genes were predicted by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and Gene Ontology (GO) analysis. HO induced G1 phase cell arrest, decreased cell viability, and upregulated the senescence marker p16 in HUVECs. We found that VC treatment inhibited G1 phase cell arrest, increased the number of cells in the S and G2/M phases, increased cell viability, and decreased p16 expression. The piRNA expression profiles revealed that a large proportion of piRNAs that were differentially expressed in HO-treated HUVECs were partly normalized by VC. Furthermore, a number of piRNAs associated with the response to VC in HO-treated HUVECs were linked with senescence and cell cycle-related pathways and networks. These results indicate that the ability of VC to attenuate HO-mediated endothelial cell senescence may be associated with changes in expression of piRNAs that are linked to the cell cycle.
维生素 C 对血管内皮细胞衰老影响的作用机制尚不清楚。为了研究 Piwi 相互作用 RNA（piRNA）是否参与这一过程，我们使用 HO 诱导人脐静脉内皮细胞（HUVEC）衰老模型，并用维生素 C（VC）处理。未暴露于 HO 的未经处理的 HUVEC 用作阴性对照组。评估细胞周期、细胞活力和衰老相关蛋白的表达，并进行 RNA 测序以揭示 piRNA 图谱。通过京都基因与基因组百科全书（KEGG）途径富集和基因本体论（GO）分析预测不同 piRNA 靶基因的功能和调控网络。HO 诱导 G1 期细胞停滞，降低细胞活力，并上调 HUVECs 中的衰老标志物 p16。我们发现 VC 处理抑制 G1 期细胞停滞，增加 S 和 G2/M 期细胞数量，增加细胞活力，并降低 p16 表达。piRNA 表达谱显示，HO 处理的 HUVECs 中差异表达的大量 piRNA 部分被 VC 正常化。此外，与 HO 处理的 HUVECs 中对 VC 反应相关的一些 piRNAs 与衰老和细胞周期相关途径和网络有关。这些结果表明，VC 减弱 HO 介导的血管内皮细胞衰老的能力可能与与细胞周期相关的 piRNA 表达变化有关。
