Downregulation of Filamin a Expression in the Aorta Is Correlated With Aortic Dissection.
Downregulation of Filamin a Expression in the Aorta Is Correlated With Aortic Dissection.
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主动脉中细丝蛋白 a 表达的下调与主动脉夹层相关
DOI：
10.3389/fcvm.2021.690846
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发表时间：
2021
影响因子：
3.6
通讯作者：
Zhu XH
中科院分区：
文献类型：
--
作者：
Chen Y;Wei X;Zhang Z;He Y;Huo B;Guo X;Feng X;Fang ZM;Jiang DS;Zhu XH
丝蛋白(flamins，Flns)是肌动蛋白的交联蛋白，作为支架蛋白与细胞骨架的稳定密切相关。然而，Flns在主动脉夹层(AD)中的生物学意义尚未得到很好的阐明。在这项研究中，我们首先重新分析了从基因表达总览(GEO)数据库下载的数据集，发现除了细胞外基质，肌动蛋白细胞骨架是与AD相关的关键结构。鉴于FLN参与重塑细胞骨架以影响细胞功能，我们测量了它们在斯坦福A型AD(TAAD)患者主动脉中的表达水平。我们的结果表明，在人和小鼠的夹层动脉中，FlnA的mRNA和蛋白水平持续下降，而FlnB的蛋白水平却在下降的情况下上调，并且组间的FlnC的表达水平相似。免疫组织化学结果显示，在非AD患者的主动脉中，Flna高表达，而在人和小鼠的主动脉中层表达下调。此外，我们还发现，形成二聚体转录因子AP-1(激活蛋白-1)的Fos和Jun与主动脉中Flna的表达呈正相关。Fos和Jun单独过表达，或FOS和Jun共同过表达均可促进原代培养的人血管内皮细胞表达Flna。在本研究中，我们不仅检测了有无AD的人和小鼠主动脉中Flns的表达模式，而且我们还发现，在AD样本中，Flna的表达显著降低，AP-1可能调节了Flna的表达。我们的发现将有助于阐明AD的发病机制，并为AD提供潜在的治疗靶点。
Filamins (FLNs) are actin cross-linking proteins, and as scaffolding proteins, FLNs are closely associated with the stabilization of the cytoskeleton. Nevertheless, the biological importance of FLNs in aortic dissection (AD) has not been well-elucidated. In this study, we first reanalyzed datasets downloaded from the Gene Expression Omnibus (GEO) database, and we found that in addition to the extracellular matrix, the actin cytoskeleton is a key structure associated with AD. Given that FLNs are involved in remodeling the cytoskeleton to affect cellular functions, we measured their expression levels in the aortas of patients with Stanford type A AD (TAAD). Our results showed that the mRNA and protein levels of FLNA were consistently decreased in dissected aortas of both humans and mice, while the FLNB protein level was upregulated despite decreased FLNB mRNA levels, and comparable expression levels of FLNC were observed between groups. Furthermore, the immunohistochemistry results demonstrated that FLNA was highly expressed in smooth muscle cells (SMCs) of aorta in non-AD samples, and downregulated in the medial layer of the dissected aortas of humans and mice. Moreover, we revealed that FOS and JUN, forming a dimeric transcription factor called AP-1 (activating protein-1), were positively correlated with the expression of FLNA in aorta. Either overexpression of FOS or JUN alone, or overexpression of FOS and JUN together, facilitated the expression of FLNA in primary cultured human aortic SMCs. In the present study, we not only detected the expression pattern of FLNs in aortas of humans and mice with or without AD, but we also found that the expression of FLNA in the AD samples was significantly reduced and that AP-1 might regulate the expression of FLNA. Our findings will contribute to the elucidation of the pathological mechanisms of AD and provide potential therapeutic targets for AD.
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影响因子：
12.4
作者：
通讯作者：
--
影响因子：
--
作者：
Chen J;Wei X;Yi X;Jiang DS
通讯作者：
Jiang DS
影响因子：
39.3
作者：
Erbel, Raimund;Aboyans, Victor;Vrints, Christiaan J. M.
通讯作者：
Vrints, Christiaan J. M.
EHMT2/G9a 通过抑制自噬激活来抑制主动脉平滑肌细胞死亡
影响因子：
9.2
作者：
Chen, Tai-Qiang;Hu, Nan;Jiang, Ding-Sheng
通讯作者：
Jiang, Ding-Sheng
影响因子：
3.7
作者：
Baldassarre M;Razinia Z;Burande CF;Lamsoul I;Lutz PG;Calderwood DA
通讯作者：
Calderwood DA