A long non-coding RNA H19/microRNA-138/TLR3 network is involved in high phosphorus-mediated vascular calcification and chronic kidney disease
A long non-coding RNA H19/microRNA-138/TLR3 network is involved in high phosphorus-mediated vascular calcification and chronic kidney disease
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长非编码RNA H19/microRNA-138/TLR3网络参与高磷介导的血管钙化和慢性肾脏疾病
DOI：
10.1080/15384101.2022.2064957
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发表时间：
2022-04-18
期刊：
影响因子：
4.3
通讯作者：
Yao, Li
中科院分区：
文献类型：
--
作者：
Liu, Qiang;Qi, Huimeng;Yao, Li
摘要血管钙化是心血管并发症和慢性肾脏病（CKD）相关死亡的主要原因，其特征是血管内钙-磷酸盐晶体的积聚。本研究主要关注CKD中高磷介导的血管钙化相关分子。采用5/6肾切除术建立慢性肾脏病大鼠模型，给予正常磷饮食（NPD）或高磷饮食（HPD）。HPD可降低肾功能，增加胸主动脉内钙离子浓度，破坏血管结构。高磷条件下血管平滑肌细胞（VSMCs）钙沉积增加。高磷还增加了主动脉组织和VSMCs中RUNX 2的表达，而降低了α-SM肌动蛋白的表达。长链非编码RNA（lncRNA）H19在HPD处理后的主动脉组织中上调。H19与microRNA（miR）-138结合，阻断其对TLR 3 mRNA的抑制作用，激活NF-κB信号通路。H19或TLR 3表达下调减轻，miR-138表达下调加重模型大鼠和VSMCs的钙化和血管损伤。总之，本研究表明，H19/miR-138/TLR 3轴参与CKD大鼠高磷介导的血管钙化。
ABSTRACT Vascular calcification, characterized by the accumulation of calcium-phosphate crystals in blood vessels, is a major cause of cardiovascular complications and chronic kidney disease (CKD)-related death. This work focuses on the molecules involved in high-phosphorus-mediated vascular calcification in CKD. A rat model of CKD was established by 5/6 nephrectomy, and the rats were given normal phosphorus diet (NPD) or high phosphorus diet (HPD). HPD decreased kidney function, increased the concentration of calcium ion and damaged vascular structure in the thoracic aorta of diseased rats. A high phosphorus condition enhanced calcium deposition in vascular smooth muscle cells (VSMCs). High phosphorus also increased the expression of RUNX2 whereas reduced the expression of α-SM actin in the aortic tissues and VSMCs. Long non-coding RNA (lncRNA) H19 was upregulated in the aortic tissues after HPD treatment. H19 bound to microRNA (miR)-138 to block its inhibitory effect on TLR3 mRNA and activated the NF-κB signaling pathway. Downregulation of H19 or TLR3 alleviated, whereas downregulation of miR-138 aggravated the calcification and vascular damage in model rats and VSMCs. In conclusion, this study demonstrates that the H19/miR-138/TLR3 axis is involved in high phosphorus-mediated vascular calcification in rats with CKD.