Upregulation of IGF2 expression during vascular calcification.
Upregulation of IGF2 expression during vascular calcification.
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血管钙化过程中 IGF2 表达上调。
DOI：
10.1530/jme-13-0136
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发表时间：
2014-04
影响因子：
3.5
通讯作者：
Macrae VE
中科院分区：
文献类型：
--
作者：
Zhu D;Mackenzie NC;Millan JL;Farquharson C;Macrae VE
血管钙化的过程与骨骼矿化的过程有许多相似之处，并且涉及动脉和心脏瓣膜中羟基磷灰石晶体的沉积。然而，负责的细胞机制尚未完全阐明。在这项研究中，我们采用微阵列分析来证明超过9000个基因在小鼠血管平滑肌细胞（VSMCs）钙化过程中的上调，其中最显着的差异表达基因是Igf 2。通过RT-qPCR和免疫印迹法验证钙化鼠VSMC中IGF 2表达增加后，进一步证实了IGF 2在Enpp 1 −/−小鼠中动脉钙化模型的钙化主动脉中的表达。已经证实IGF 1 R和IGF 2 R在培养的小鼠VSMCs中表达，在这些细胞中的细胞信号研究显示IGF 2（50 ng/ml）显著刺激Akt和Erk 1/2的磷酸化（P<0.05）。这些结果可能表明，IGF 2可能介导VSMC钙化通过刺激Erk 1/2和Akt信号。这项研究表明，钙化VSMC中IGF 2表达的增加可能反映了IGF 2在产前的良好作用，特别是钙化环境中VSMC的成骨表型转变重演了胚胎发育过程中发生的许多事件。充分了解IGF 2在这一病理过程中的重要性将有助于更好地了解血管钙化的病因。
The process of vascular calcification shares many similarities with that of skeletal mineralisation and involves the deposition of hydroxyapatite crystals in arteries and cardiac valves. However, the cellular mechanisms responsible have yet to be fully elucidated. In this study, we employed microarray analysis to demonstrate the upregulation of more than >9000 genes during the calcification of murine vascular smooth muscle cells (VSMCs), of which the most significantly, differentially expressed gene was Igf2. Following the validation of increased IGF2 expression by RT-qPCR and immunoblotting in calcifying murine VSMCs, IGF2 expression was further demonstrated in the calcified aorta of the Enpp1−/− mouse model of medial aortic calcification. Having confirmed that IGF1R and IGF2R were expressed in cultured murine VSMCs, cell-signalling studies in these cells revealed that IGF2 (50 ng/ml) significantly stimulated the phosphorylation of Akt and Erk1/2 (P<0.05). These results potentially indicate that IGF2 may mediate VSMC calcification via the stimulation of Erk1/2 and Akt signalling. This study suggests that the increased IGF2 expression in calcifying VSMCs may reflect the well-established prenatal role of IGF2, particularly as the osteogenic phenotypic transition of VSMCs in a calcified environment recapitulates many of the events occurring during embryonic development. A full understanding of the importance of IGF2 in this pathological process will lead to a better understanding of the aetiology of vascular calcification.