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长链非编码 RNA 在血管平滑肌细胞中调节血管钙化。

Long noncoding RNAs in vascular smooth muscle cells regulate vascular calcification.

机构信息

Basic Research Laboratory for Cardiac Remodeling Research Laboratory, Chonnam National University Medical School, Jeollanam-do, Republic of Korea.

Department of Biochemistry, Chonnam National University Medical School, Hwasun, Jeollanam-do, 58128, Republic of Korea.

出版信息

Sci Rep. 2019 Apr 10;9(1):5848. doi: 10.1038/s41598-019-42283-x.

DOI:10.1038/s41598-019-42283-x
PMID:30971745
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6458154/
Abstract

Vascular calcification is characterized by the accumulation of hydroxyapatite crystals, which is a result of aberrant mineral metabolism. Although many clinical studies have reported its adverse effects on cardiovascular morbidity, the molecular mechanism of vascular calcification, especially the involvement of long noncoding RNAs (lncRNAs), is not yet reported. From the transcriptomic analysis, we discovered hundreds of lncRNAs differentially expressed in rat vascular smooth muscle cells (VSMCs) treated with inorganic phosphate, which mimics vascular calcification. We focused on Lrrc75a-as1 and elucidated its transcript structure and confirmed its cytoplasmic localization. Our results showed that calcium deposition was elevated after knockdown of Lrrc75a-as1, while its overexpression inhibited calcium accumulation in A10 cells. In addition, Lrrc75a-as1 attenuated VSMCs calcification by decreasing the expression of osteoblast-related factors. These findings suggest that Lrrc75a-as1 acts as a negative regulator of vascular calcification, and may serve as a possible therapeutic target in vascular calcification.

摘要

血管钙化的特征是羟基磷灰石晶体的积累，这是矿物质代谢异常的结果。尽管许多临床研究已经报道了它对心血管发病率的不良影响，但血管钙化的分子机制，特别是长链非编码 RNA（lncRNA）的参与，尚未报道。从转录组分析中，我们在用无机磷酸盐处理的大鼠血管平滑肌细胞（VSMCs）中发现了数百个差异表达的 lncRNA，这模拟了血管钙化。我们专注于 Lrrc75a-as1，并阐明了其转录结构并确认其细胞质定位。我们的结果表明，Lrrc75a-as1 敲低后钙沉积增加，而过表达则抑制 A10 细胞中钙的积累。此外，Lrrc75a-as1 通过降低成骨细胞相关因子的表达来减轻 VSMCs 的钙化。这些发现表明 Lrrc75a-as1 作为血管钙化的负调节剂发挥作用，并且可能成为血管钙化的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6783/6458154/e999490069c9/41598_2019_42283_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6783/6458154/6dda9e970a02/41598_2019_42283_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6783/6458154/e1e28a7e19ac/41598_2019_42283_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6783/6458154/9c5a8146d015/41598_2019_42283_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6783/6458154/d9d33b9b40e6/41598_2019_42283_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6783/6458154/e999490069c9/41598_2019_42283_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6783/6458154/6dda9e970a02/41598_2019_42283_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6783/6458154/e1e28a7e19ac/41598_2019_42283_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6783/6458154/9c5a8146d015/41598_2019_42283_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6783/6458154/d9d33b9b40e6/41598_2019_42283_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6783/6458154/e999490069c9/41598_2019_42283_Fig5_HTML.jpg

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