Xia Hou-Fu, Ren Jian-Gang, Zhu Jun-Yi, Yu Zi-Li, Zhang Wei, Sun Yan-Fang, Zhao Yi-Fang, Chen Gang
The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China; Department of Oral and Maxillofacial Surgery, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
Eur J Pharm Sci. 2017 Mar 30;100:126-131. doi: 10.1016/j.ejps.2017.01.019. Epub 2017 Jan 16.
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, and α-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 in HUVECs 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.
静脉畸形（VMs）的特征是扩张迂曲的静脉通道，其血管周围细胞覆盖减少。最近的研究发现，miR-145通过调节血管平滑肌细胞（VSMCs）的分化和表型，在多种血管疾病中发挥关键作用。然而，miR-145在VMs中的潜在作用仍不清楚。在本研究中，收集了21例无治疗史的VMs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）评估转化生长因子-β（TGF-β）、miR-145和α-平滑肌肌动蛋白（α-SMA）的表达水平。随后，使用Spearman等级相关检验分析它们之间的相关性。体外研究使用人脐静脉内皮细胞（HUVECs）进行。结果显示，与正常皮肤组织相比，VMs中miR-145显著下调，同时TGF-β表达水平和血管周围α-SMA细胞覆盖同步降低。相关性分析显示，VMs中miR-145表达与TGF-β表达和血管周围α-SMA细胞覆盖呈正相关。此外，在用博来霉素A5治疗的VMs组织中，TGF-β、miR-145和α-SMA同时增加。更重要的是，体外研究表明，重组人TGF-β和博来霉素A5均可显著上调HUVECs中TGF-β和miR-145的表达，且增加趋势相似。总之，我们目前的研究揭示了VMs中miR-145的下调，可能由TGF-β抑制诱导，并与血管紊乱密切相关。此外，miR-145可能参与VMs的硬化治疗并具有靶向潜力。
