title: MiR-126 inhibits vascular endothelial cell apoptosis through targeting PI3K/Akt signaling.
abstract: BACKGROUND
  MiR-126 is likely to be closely associated with the threatening disease deep venous thrombosis (DVT).
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Overexpressed miR-126 inhibits apoptosis of VECs and DVT through targeting the anti-apoptotic pathway PI3K/Akt via PIK3R2.
  
  
  CONCLUSIONS
  These findings may provide a new target for the therapy of DVT.
authors.affiliation: Department of Orthopaedics, First Affiliated Hospital of Kunming Medical University, Xichang Road No. 295, Kunming, Yunnan Province, 650032, China.
authors.forename: Lingqiang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Rheumatology and Immunology, First People's Hospital of Yunnan Province, Jinbi Road, No. 157, Kunming, Yunnan Province, 650032, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, First Affiliated Hospital of Kunming Medical University, Xichang Road No. 295, Kunming, Yunnan Province, 650032, China. bingwang0@126.com.
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, First Affiliated Hospital of Kunming Medical University, Xichang Road No. 295, Kunming, Yunnan Province, 650032, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Orthopaedics, First Affiliated Hospital of Kunming Medical University, Xichang Road No. 295, Kunming, Yunnan Province, 650032, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Gong
authors.affiliation: Department of Orthopaedics, First Affiliated Hospital of Kunming Medical University, Xichang Road No. 295, Kunming, Yunnan Province, 650032, China.
authors.forename: Xueling
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Orthopaedics, First Affiliated Hospital of Kunming Medical University, Xichang Road No. 295, Kunming, Yunnan Province, 650032, China.
authors.forename: Chunqiang
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, First Affiliated Hospital of Kunming Medical University, Xichang Road No. 295, Kunming, Yunnan Province, 650032, China.
authors.forename: Kaili
authors.initials: K
authors.lastname: Du
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; C571458:MIRN126 microRNA, rat
keywords: Akt; Deep venous thrombosis (DVT); MicroRNA miR-126; PI3K; Vascular endothelial cell (VEC) injury