Downregulation of miR-145 in Venous Malformations: Its Association with Disorganized Vessels and Sclerotherapy
Downregulation of miR-145 in Venous Malformations: Its Association with Disorganized Vessels and Sclerotherapy
复制标题
静脉畸形中 miR-145 的下调：与血管紊乱和硬化疗法的关系
DOI：
10.1016/j.ejps.2017.01.019
复制
发表时间：
2017
影响因子：
4.6
通讯作者：
Gang Chen
中科院分区：
文献类型：
--
作者：
Houfu Xia;Jiangang Ren;Junyi Zhu;Zili Yu;Wei Zhang;Yanfang Sun;Yifang Zhao;Gang Chen
静脉畸形（VM）的特征是静脉通道扩张和迂曲，血管周围细胞覆盖减少。近年来研究发现，miR-145通过调节血管平滑肌细胞（VSMC）的分化和表型，在多种血管疾病中发挥重要作用。然而，miR-145在VM中的潜在作用仍然未知。在这项研究中，收集了21例无治疗史的VM样本和10例健康供体皮肤样本，通过免疫组织化学、原位杂交和实时聚合酶链反应（PCR）来评估TGF-β、miR-145和α-SMA的表达水平。随后，使用斯皮尔曼等级相关检验分析它们的相关性。使用人脐静脉内皮细胞（HUVEC）进行体外研究。结果显示，与正常皮肤组织相比，VM组织中miR-145表达显著下调，同时伴有TGF-β表达水平和血管周围α-SMA+细胞覆盖率的同步下降。相关分析显示，VM中miR-145表达与TGF-β表达和血管周围α-SMA+细胞覆盖率呈正相关。此外，在用博来霉素A5处理的VM的组织中，TGF-β、miR-145和α-SMA同时增加。更重要的是，体外研究发现，重组人TGF-β和博来霉素A5均能显著上调HUVECs中TGF-β和miR-145的表达，且上调趋势相似。总之，我们目前的研究揭示了VM中miR-145的下调，可能是由TGF-β抑制诱导的，并与紊乱的血管密切相关。此外，miR-145可能参与VM的硬化治疗，具有靶向作用潜力。
Venous malformations (VMs) are characterized by ectatic and tortuous venous channels with decreased perivascular cell coverage. Recent studies have discovered that miR-145 plays a critical role in amounts of vascular diseases through regulating the differentiation and phenotype of vascular smooth muscle cells (VSMCs). However, the potential roles of miR-145 in VMs remain unknown. In this study, 21 samples of VMs without treatment history, and 10 samples of healthy donor skin were collected to evaluate the expression level of TGF-β, miR-145, andα-SMA by immunohistochemistry, in situ hybridization, and real-time polymerase chain reaction (PCR). Subsequently, their correlations were analyzed using the Spearman rank correlation test. In vitro studies were performed using human umbilical vein endothelial cells (HUVECs). The results showed that miR-145 was significantly downregulated in VMs compared with normal skin tissues, accompanied by a synchronously decreased TGF-β expression level and perivascular α-SMA+ cell coverage. Correlation analysis revealed that miR-145 expression was positively correlated with TGF-β expression and perivascular α-SMA+ cell coverage in VMs. In addition, TGF-β, miR-145, and α-SMA were concurrently increased in the tissues of VMs treated with bleomycin A5. More importantly, in vitro studies revealed that both recombinant human TGF-β and bleomycin.A5 could significantly upregulate TGF-β and miR-145 expression inHUVECs with the similar increasing tendency. In summary, our present study unmasked the downregulation of miR-145 in VMs, possibly induced by TGF-β depression and closely correlated with disorganized vessels. Moreover, miR-145 may be involved in the sclerotherapy of VMs and possess the target potential..