Department of Nephrology, Beijing Friendship Hospital, Faculty of Kidney Diseases, Capital Medical University, Beijing, China.
Ren Fail. 2020 Nov;42(1):437-446. doi: 10.1080/0886022X.2020.1758722.
Cardiovascular events are the primary cause of death for chronic kidney disease patients, which occurred vascular calcification evolving pathogenically. Although a high level of phosphorus contributes to the induction of osteogenic differentiation of vascular smooth muscle cells (VSMCs), the role of lncRNA in this process awaits further study. In this study, we systematically investigated the variation of gene expression in human VSMCs induced by high phosphorus. LncRNAs and mRNAs expression were revealed by microarray analyses of the control group and high-phosphorus (HP) group. LncRNA-mRNA co-expression network was established based on the specific lncRNA-mRNA relationships. Hierarchical clustering was used to identify a common set of regulated genes. In addition, Gene Ontology enrichment, Kyoto Gene-Encyclopedia and genomic analyses were conducted for the mRNAs differentially expressed under high phosphorus. RT-qPCR results confirmed that the expression of RUNX2, BMP2 and osteocalcin in HP group exhibited significant increases than in control group ( < .05). VSMC in HP group also showed higher intracellular calcium content. Volcano plots results show that 379 mRNAs and 728 lncRNAs different expressed in HP group. LncRNA-mRNA co-expression networks analysis revealed that 8 lncRNAs were the most highly connected lncRNAs. Quantitative analysis indicated that two lncRNAs were confirmed to increase significantly in the HP group. The mRNA expression of NT5E and ICAM1 were higher in group HP, while MAP3K7CL was lower than CON group ( < .05). This study provided a working list of lncRNAs that may be relevant to osteogenic differentiation, which presents a new insights into the mechanism of vascular calcification induced by high phosphorus in VSMCs.
心血管事件是慢性肾脏病患者的主要死亡原因，其发生与血管钙化的病理演变有关。虽然高水平的磷有助于诱导血管平滑肌细胞（VSMCs）的成骨分化，但 lncRNA 在这一过程中的作用仍有待进一步研究。在这项研究中，我们系统地研究了高磷诱导的人 VSMCs 中的基因表达变化。通过对对照组和高磷（HP）组的微阵列分析，揭示了 lncRNA 和 mRNA 的表达。基于特定的 lncRNA-mRNA 关系，建立了 lncRNA-mRNA 共表达网络。层次聚类用于识别一组共同调控的基因。此外，对高磷条件下差异表达的 mRNAs 进行了基因本体论富集、京都基因百科全书和基因组分析。RT-qPCR 结果证实，HP 组中 RUNX2、BMP2 和骨钙素的表达明显高于对照组（ < .05）。HP 组的 VSMC 也表现出更高的细胞内钙含量。火山图结果显示，HP 组有 379 个 mRNAs 和 728 个 lncRNAs 差异表达。lncRNA-mRNA 共表达网络分析显示，8 个 lncRNAs是连接性最高的 lncRNAs。定量分析表明，有两个 lncRNAs在 HP 组中显著增加。HP 组中 NT5E 和 ICAM1 的 mRNA 表达较高，而 MAP3K7CL 则低于 CON 组（ < .05）。这项研究提供了一个可能与成骨分化相关的 lncRNAs 工作列表，为高磷诱导 VSMCs 血管钙化的机制提供了新的见解。
