miRNA-221 and miRNA-222 synergistically function to promote vascular calcification.

miRNA-221 and miRNA-222 synergistically function to promote vascular calcification.
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DOI:
10.1002/cbf.3005
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发表时间:
2014-03
影响因子:
3.6
通讯作者:
MacRae, V. E.
MacRae, V. E.
中科院分区:
生物学3区
文献类型:
--
作者:
Mackenzie, N. C. W.;Staines, K. A.;Zhu, D.;Genever, P.;MacRae, V. E.

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血管钙化与骨骼矿化有许多相似之处,涉及在钙化环境中血管平滑肌细胞(VSMCs)向成骨细胞的表型转分化。已知多种microRNAs(MiRs)调节细胞分化,然而,它们在介导VSMC钙化中的作用尚不完全清楚。MIR芯片分析显示,培养9天后,一系列miR显著下调,包括miR-199b、miR-29a、miR-221、miR-222和miR-31(p&lt;0.05)。随后的研究调查了miR-221/222家族在VSMC钙化中的具体作用。实时定量聚合酶链式反应数据证实miR-221(32.4%;p<0.01)和miR-222(15.7%;p&lt;0.05)表达下调。将miR-221和miR-222的模拟物分别和联合导入VSMC。在联合治疗中观察到钙沉积增加(两倍;p&lt;0.05),但在单独治疗中没有。Runx2和MSX2在钙化过程中表达增加,但经miR模拟体转染后表达无差异。有趣的是,miR-221和miR-222模拟物诱导了胞外核苷酸磷酸二酯酶1(Enpp1)和Pit-1表达的显著变化,提示这些miR可能通过细胞内无机磷和焦磷水平来调节VSMC的钙化。©2013作者。《细胞生物化学与功能》由John Wiley&Sons,Ltd.出版。
Vascular calcification shares many similarities with skeletal mineralisation and involves the phenotypic trans-differentiation of vascular smooth muscle cells (VSMCs) to osteoblastic cells within a calcified environment. Various microRNAs (miRs) are known to regulate cell differentiation; however, their role in mediating VSMC calcification is not fully understood. miR-microarray analysis revealed the significant down-regulation of a range of miRs following nine days in culture, including miR-199b, miR-29a, miR-221, miR-222 and miR-31 (p < 0.05). Subsequent studies investigated the specific role of the miR-221/222 family in VSMC calcification. Real-time quantitative polymerase chain reaction data confirmed the down-regulation of miR-221 (32.4%; p < 0.01) and miR-222 (15.7%; p < 0.05). VSMCs were transfected with mimics of miR-221 and miR-222, individually and in combination. Increased calcium deposition was observed in the combined treatment (two-fold; p < 0.05) but not in individual treatments. Runx2 and Msx2 expression was increased during calcification, but no difference in expression was observed following transfection with miR mimics. Interestingly, miR-221 and miR-222 mimics induced significant changes in ectonucleotide phosphodiesterase 1 (Enpp1) and Pit-1 expression, suggesting that these miRs may modulate VSMC calcification through cellular inorganic phosphate and pyrophosphate levels. © 2013 The Authors. Cell Biochemistry and Function published by John Wiley & Sons, Ltd.
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