Chen Gang, Ren Jian-Gang, Zhang Wei, Sun Yan-Fang, Wang Feng-Qin, Li Rui-Fang, Zhang Jian, Zhao Yi-Fang
1] 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 [2] Department of Oral and Maxillofacial Surgery, School & Hospital of Stomatology, Wuhan University, Wuhan, China [3].
1] 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 [2].
Sci Rep. 2014 Jun 26;4:5457. doi: 10.1038/srep05457.
Venous malformations (VMs) are among the most common slow-flow vascular malformations characterized by irregular venous channels, luminal thrombi, and phleboliths. To systematically manifest the disorganized vascular structures in sporadic VMs, we initially evaluated histopathological characteristics, perivascular cell coverage, adhesion molecules expression and vascular ultrastructures. Then, the expression of Tie2 and TGF-β in VMs was detected. Meanwhile, the in vitro studies were performed for mechanism investigation. Our data showed that the perivascular α-SMA(+) cell coverage and expression of adhesion molecules in VMs were significantly decreased compared with those in the normal skin tissues. We also found that the expression and phosphorylation levels of Tie2 were upregulated, whereas TGF-β was downregulated in VMs, and they were negatively correlated. Moreover, the in vitro results also revealed a possible balancing effect between Tie2 and TGF-β, as demonstrated by the findings that Ang-1 (agonist of Tie2) treatment significantly downregulated TGF-β expression, and treatment with recombinant TGF-β could also suppress Tie2 expression and phosphorylation. This study provided strong evidence supporting the disorganized vascular structures and dysregulation of related molecules in sporadic VMs, and demonstrated a possible balancing effect between Tie2 and TGF-β, which might help to develop novel therapeutics for vascular disorganization-related disorders.
静脉畸形（VMs）是最常见的缓慢血流性血管畸形之一，其特征为不规则的静脉通道、管腔内血栓和静脉石。为了系统地呈现散发性VMs中紊乱的血管结构，我们首先评估了组织病理学特征、血管周围细胞覆盖情况、黏附分子表达和血管超微结构。然后，检测了VMs中Tie2和TGF-β的表达。同时，进行了体外研究以探究机制。我们的数据显示，与正常皮肤组织相比，VMs中血管周围α-SMA(+)细胞覆盖和黏附分子表达显著降低。我们还发现，VMs中Tie2的表达和磷酸化水平上调，而TGF-β下调，且二者呈负相关。此外，体外研究结果还揭示了Tie2和TGF-β之间可能存在平衡作用，如Ang-1（Tie2激动剂）处理显著下调TGF-β表达，重组TGF-β处理也可抑制Tie2表达和磷酸化的结果所示。本研究提供了有力证据支持散发性VMs中血管结构紊乱和相关分子失调，并证明了Tie2和TGF-β之间可能存在平衡作用，这可能有助于开发针对血管紊乱相关疾病的新型疗法。
