Zhang Hongxing, Sun Xiaojuan, Hao Dingjun
Department of Hand Surgery, Xi'an Honghui Hospital, Xi'an Jiaotong University Health Science Center, Xi'an 710054, China.
Department of Anesthesiology, Xi'an Honghui Hospital, Xi'an Jiaotong University Health Science Center, Xi'an 710054, China.
Exp Biol Med (Maywood). 2016 Feb;241(3):282-9. doi: 10.1177/1535370215600549. Epub 2015 Aug 27.
Angiogenesis is critical to the success of digital replantation. Recent study suggests an important regulatory role of microRNA-370 (miR-370) in ischemia-reperfusion injury. However, its function in digital replantation is poorly understood. In this study, we reported that the expression of miR-370 was upregulated in replantation tissues. miR-370 mimic transfection promoted human umbilical vein endothelial cells (HUVECs) proliferation by regulating the cell cycle and inhibited apoptosis. miR-370 mimic transfection also significantly increased HUVECs migration and induced the formation of capillary-like structures in HUVECs, indicated that miR-370 promoted capillary tube formation in vitro. Furthermore, forkhead box protein O1 (FOXO1) was identified as the functional target of miR-370 by dual-luciferase reporter assay. FOXO1 overexpression vector lacked 3'-UTR together with miR-370 mimic transfection strongly abrogated miR-370-induced cell proliferation and the formation of capillary-like structures in HUVECs. Taken together, our results revealed that the upregulation of miR-370 might facilitate the repair of amputated fingers by regulating angiogenesis through targeting FOXO1. This study provided a potential therapeutic target for the restoration of finger function after replantation.
血管生成对于断指再植的成功至关重要。最近的研究表明,微小RNA-370(miR-370)在缺血再灌注损伤中起重要调节作用。然而,其在断指再植中的功能尚不清楚。在本研究中,我们发现miR-370在再植组织中的表达上调。miR-370模拟物转染通过调节细胞周期促进人脐静脉内皮细胞(HUVECs)增殖并抑制细胞凋亡。miR-370模拟物转染还显著增加了HUVECs的迁移,并诱导了HUVECs中毛细血管样结构的形成,表明miR-370在体外促进了毛细血管管的形成。此外,通过双荧光素酶报告基因检测确定叉头框蛋白O1(FOXO1)为miR-370的功能靶点。FOXO1过表达载体缺失3'-UTR,与miR-370模拟物转染一起强烈消除了miR-370诱导的细胞增殖和HUVECs中毛细血管样结构的形成。综上所述,我们的结果表明,miR-370的上调可能通过靶向FOXO1调节血管生成来促进断指的修复。本研究为再植后手指功能恢复提供了一个潜在的治疗靶点。