MiR-126 inhibits vascular endothelial cell apoptosis through targeting PI3K/Akt signaling

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• 作者：Lingqiang Chen ; Jing Wang ; Bing Wang ; Jin Yang ; Zhiqiang Gong…
• 关键词：Deep venous thrombosis (DVT) ; Vascular endothelial cell (VEC) injury ; MicroRNA miR ; 126 ; PI3K ; Akt
• 刊名：Annals of Hematology
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：95
• 期：3
• 页码：365-374
• 全文大小：1,358 KB
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• 作者单位：Lingqiang Chen (1)
  Jing Wang (2)
  Bing Wang (1)
  Jin Yang (1)
  Zhiqiang Gong (1)
  Xueling Zhao (1)
  Chunqiang Zhang (1)
  Kaili Du (1)
  
  1. Department of Orthopaedics, First Affiliated Hospital of Kunming Medical University, Xichang Road No. 295, Kunming, Yunnan Province, 650032, China
  2. Department of Rheumatology and Immunology, First People’s Hospital of Yunnan Province, Jinbi Road, No. 157, Kunming, Yunnan Province, 650032, China
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Hematology
  Oncology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-0584

文摘

Background: MiR-126 is likely to be closely associated with the threatening disease deep venous thrombosis (DVT). Aim: This study aims to investigate the influence of aberrantly expressed miR-126 on vascular endothelial cell (VEC) apoptosis during DVT and explore how miR-126 functions in it. Methods: MiR-126 inhibition and overexpression in vivo were respectively performed with antagomir and agomir of miR-126. Using a rat traumatic femoral DVT model, VEC apoptosis and miR-126 expression were detected by TUNEL assay and qRT-PCR before thrombogenesis and at different time phases of thrombogenesis. Protein levels of MMPs, Akt, Bcl-2, Bad, and caspase-9 in vascular tissue were measured by western blotting. In vitro, miR-126 interference, and overexpression were performed on human umbilical vein endothelial cells (HUVECs) using miR-126 inhibitor and mimics. After HUVECs were pretreated with CoCl₂, cell apoptosis was analyzed using flow cytometry, and RNA/protein levels of miR-126, PIK3R2, PTEN, and phosphorylated Akts were measured with qRT-PC/western blotting. Results: The apoptosis of VECs was increased by miR-126 inhibition and obviously rescued by miR-126 overexpression. PI3K/Akt signal transduction was suppressed by miR-126 inhibition and evidently enhanced by miR-126 overexpression. Consistent with these findings, the downstream proteins (Bcl-2, Bad, and cleaved caspase-9) in PI3K/Akt pathway and the MMPs were remarkably changed by inhibition or overexpression of miR-126. In vitro experiments also showed that PI3K/Akt signaling was strengthened when miR-126 expression was upregulated or inhibited when miR-126 was knockdown. Conclusion: Overexpressed miR-126 inhibits apoptosis of VECs and DVT through targeting the anti-apoptotic pathway PI3K/Akt via PIK3R2. General significance: These findings may provide a new target for the therapy of DVT. Keywords Deep venous thrombosis (DVT) Vascular endothelial cell (VEC) injury MicroRNA miR-126 PI3K Akt