Inorganic phosphate accelerates the migration of vascular smooth muscle cells: evidence for the involvement of miR-223.
Inorganic phosphate accelerates the migration of vascular smooth muscle cells: evidence for the involvement of miR-223.
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DOI：
10.1371/journal.pone.0047807
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Metzinger L
中科院分区：
文献类型：
--
作者：
Rangrez AY;M'Baya-Moutoula E;Metzinger-Le Meuth V;Hénaut L;Djelouat MS;Benchitrit J;Massy ZA;Metzinger L
血清无机磷酸盐（Pi）水平升高是肾脏疾病和下游血管并发症的主要风险因素。我们专注于Pi水平对人主动脉血管平滑肌细胞（VSMCs）的影响，重点是microRNA（miRNAs）的作用。暴露于病理水平的Pi的人原代VSMCs在体外增加钙化，迁移率，并伴随着减少细胞增殖和肌动蛋白细胞骨架的量。这些变化通过miRNA-143（miR-143）和miR-145的显著下调以及其靶点和合成VSMC中的关键标志物（如Krüppel样因子-4和-5和多功能蛋白聚糖）的伴随上调来证明。有趣的是，我们还发现miR-223（肌肉损伤的标志物和破骨细胞分化的关键因子）在VSMC中表达，并且在Pi处理的细胞中显著上调。在VSMC中过表达miR-223增加增殖并显著增强VSMC迁移。此外，我们发现两个已知的miR-223靶点Mef 2c和RhoB的表达在Pi处理的以及miR-223过表达的VSMC中高度降低。为了补充这些体外研究结果，我们还观察到从ApoE敲除小鼠收集的主动脉样本中miR-143和miR-145的显著下调以及miR-223的上调，这些样本显示血管钙化。我们的研究结果表明，（i）高水平的Pi增加VSMC迁移和钙化，（ii）miR-223的表达水平改变可能在此过程中发挥作用，（iii）miR-223是VSMC损伤的潜在新生物标志物。
An elevated serum inorganic phosphate (Pi) level is a major risk factor for kidney disease and downstream vascular complications. We focused on the effect of Pi levels on human aortic vascular smooth muscle cells (VSMCs), with an emphasis on the role of microRNAs (miRNAs). Exposure of human primary VSMCs in vitro to pathological levels of Pi increased calcification, migration rate and concomitantly reduced cell proliferation and the amount of the actin cytoskeleton. These changes were evidenced by significant downregulation of miRNA-143 (miR-143) and miR-145 and concomitant upregulation of their targets and key markers in synthetic VSMCs, such as Krüppel-like factors−4 and −5 and versican. Interestingly, we also found that miR-223 (a marker of muscle damage and a key factor in osteoclast differentiation) is expressed in VSMCs and is significantly upregulated in Pi-treated cells. Over-expressing miR-223 in VSMCs increased proliferation and markedly enhanced VSMC migration. Additionally, we found that the expression of two of the known miR-223 targets, Mef2c and RhoB, was highly reduced in Pi treated as well as miR-223 over-expressing VSMCs. To complement these in vitro findings, we also observed significant downregulation of miR-143 and miR-145 and upregulation of miR-223 in aorta samples collected from ApoE knock-out mice, which display vascular calcification. Our results suggest that (i) high levels of Pi increase VSMC migration and calcification, (ii) altered expression levels of miR-223 could play a part in this process and (iii) miR-223 is a potential new biomarker of VSMC damage.
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影响因子：
64.8
作者：
Cordes KR;Sheehy NT;White MP;Berry EC;Morton SU;Muth AN;Lee TH;Miano JM;Ivey KN;Srivastava D
通讯作者：
Srivastava D
影响因子：
64.8
作者：
Johnnidis, Jonathan B.;Harris, Marian H.;Camargo, Fernando D.
通讯作者：
Camargo, Fernando D.
影响因子：
15.9
作者：
Boettger, Thomas;Beetz, Nadine;Braun, Thomas
通讯作者：
Braun, Thomas
DOI：
10.1083/jcb.50.1.172
发表时间：
1971-07
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ross R
通讯作者：
Ross R
影响因子：
4
作者：
Sugatani, T.;Hruska, K. A.
通讯作者：
Hruska, K. A.