Downregulation of miR-145 in venous malformations: Its association with disorganized vessels and sclerotherapy

Abstract

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.

Keywords: Bleomycin A5; TGF-β; Venous malformations; miR-145.