Spatiotemporal expression of matrix metalloproteinases (MMPs) is regulated by the Ca2+-signal transducer S100A4 in the pathogenesis of thoracic aortic aneurysm.
Spatiotemporal expression of matrix metalloproteinases (MMPs) is regulated by the Ca2+-signal transducer S100A4 in the pathogenesis of thoracic aortic aneurysm.
复制标题
胸主动脉瘤发病机制中基质金属蛋白酶 (MMP) 的时空表达受 Ca2 信号转导器 S100A4 的调节
DOI：
10.1371/journal.pone.0070057
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Chen Y
中科院分区：
文献类型：
--
作者：
Cao J;Geng L;Wu Q;Wang W;Chen Q;Lu L;Shen W;Chen Y
目的探讨S100A4是否在胸主动脉瘤（TAA）形成中起潜在作用。方法与结果雄性Sprague-Dawley大鼠胸主动脉灌注0.5 M CaCl2或生理盐水（NaCl）。动物在指定时间点（taa诱导后2、4和10周）实施安乐死。采集处理后的主动脉段，分析MMP-2、MMP-9和S100A4 mRNA水平、蛋白表达和免疫组化。A7r5细胞系用于体外研究。实验还使用人类TAA样本进行比较。在cacl2处理的节段中观察到局部动脉瘤扩张。与对照组相比，cacl2处理的片段中S100A4和MMPs的转录水平升高，并且在所有时间点观察到S100A4和MMPs表达之间的显著相关性。免疫组化研究显示S100A4与MMP蛋白表达模式相似，且S100A4与细胞谱系标志物（αSMA和CD68）和炎症标志物（MMPs和NF-κB P65亚基）共定位。转染S100A4 siRNA后，A7r5细胞的增殖能力受到抑制，下调S100A4可抑制体外MMP-2和MMP-9的表达。人TAA标本主动脉壁各层均可见S100A4表达增高。ELISA测定的血清S100A4浓度在TAA患者中显著升高。结论本研究确定了S100A4和MMPs在TAA发生中的重要作用。
Aims This study investigated whether S100A4 plays a potential role in the formation of thoracic aortic aneurysm (TAA). Methods and Results The thoracic aortas of male Sprague-Dawley rats were exposed to 0.5 M CaCl2 or normal saline (NaCl). Animals were euthanized at specified time-points (2, 4, and 10 weeks post-TAA induction). The treated aortic segments were harvested, and mRNA levels, protein expressions and immunohistochemistry of MMP-2, MMP-9 and S100A4 were analyzed. The A7r5 cell lines were used for an in vitro study. Experiments were also performed using human TAA samples for comparison. Localized aneurysmal dilation was observed in the CaCl2-treated segments. The transcription levels of S100A4 and MMPs were elevated in CaCl2-treated segments versus controls, and a significant correlation between S100A4 and expression of MMPs was observed across all time-points. Immunohistochemical studies revealed similar expression pattern of S100A4 and MMP proteins, as well as co-localization of S100A4 with the cell lineage markers (αSMA and CD68) and inflammatory markers (MMPs and NF-κB P65 subunit). The proliferative ability of A7r5 cells after transfection with S100A4 siRNA was suppressed, and down-regulation of S100A4 inhibited MMP-2 and MMP-9 expression in vitro. Increased expression of S100A4 was observed in all layers of the aorta wall in human TAA specimens. Serum concentrations of S100A4 determined by ELISA were found to be significantly increased in TAA patients. Conclusions This study established the important roles of S100A4 and MMPs in the development of TAA.
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影响因子：
15.9
作者：
Longo, GM;Xiong, WF;Baxter, BT
通讯作者：
Baxter, BT
影响因子：
20.1
作者：
Chung, Ada W. Y.;Yang, H. H. Clarice;van Breemen, Cornelis
通讯作者：
van Breemen, Cornelis
影响因子：
4.3
作者：
Xiong, Wanfen;Knispel, Rebecca A.;Baxter, Timothy
通讯作者：
Baxter, Timothy
影响因子：
20.1
作者：
Brisset, Anne C.;Hao, Hiroyuki;Bochaton-Piallat, Marie-Luce
通讯作者：
Bochaton-Piallat, Marie-Luce
影响因子：
37.8
作者：
Kuivaniemi, Helena;Platsoucas, Chris D.;Tilson, M. David, III
通讯作者：
Tilson, M. David, III