title: Hypoxia-induced deregulation of miR-126 and its regulative effect on VEGF and MMP-9 expression.
abstract: OBJECTIVE
  miR-126, the miRNA considered to be specially expressed in endothelial cells and hematopoietic progenitor cells, is strongly associated with angiogenesis. The purpose is to evaluate the role of miR-126 in hypoxia-induced angiogenesis and the possible mechanisms.
  
  
  METHODS
  The expression of miR-126 was detected in hypoxia-treated RF/6A cells and diabetic retinas using real-time PCR. The miR-126 was up- or down-regulated by transfecting miR-126-mimics or inhibitors into RF/6A cells. Cell cycle analysis was performed using flow cytometry. The protein levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) were assessed by immunoblotting.
  
  
  RESULTS
  A significantly decreased expression of miR-126 was found in hypoxia-treated RF/6A cells in a time-dependent manner compared with normoxic condition. The expression of miR-126 was also reduced in the retina tissue of streptozotocin-induced diabetic rats. The expression of VEGF and MMP-9 proteins was increased in hypoxia-induced RF/6A cells. In the functional analysis, miR-126-mimic significantly reduced the percentage of RF/6A cells in S phases compared with the negative control under hypoxic conditions. Furthermore, the VEGF and MMP-9 protein levels were sharply decreased in hypoxia-induced RF/6A cells pretreated with miR-126-mimics and increased in the cells pretreated with miR-126-inhibitors.
  
  
  CONCLUSIONS
  miR-126 is down-regulated under hypoxic condition both in vitro and in vivo and may halt the hypoxia-induce neovascularization by suspending the cell cycle progression and inhibiting the expression of VEGF and MMP-9.
authors.affiliation: 1. Eye Center, Second Affiliated Hospital, School of Medicine, Zhejiang University; ; 2. Zhejiang Provincial Key Lab of Ophthalmology, China.
authors.forename: Panpan
authors.initials: P
authors.lastname: Ye
authors.affiliation: 1. Eye Center, Second Affiliated Hospital, School of Medicine, Zhejiang University; ; 2. Zhejiang Provincial Key Lab of Ophthalmology, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.affiliation: 1. Eye Center, Second Affiliated Hospital, School of Medicine, Zhejiang University; ; 2. Zhejiang Provincial Key Lab of Ophthalmology, China.
authors.forename: Fengying
authors.initials: F
authors.lastname: He
authors.affiliation: 1. Eye Center, Second Affiliated Hospital, School of Medicine, Zhejiang University; ; 2. Zhejiang Provincial Key Lab of Ophthalmology, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Xu
authors.affiliation: 1. Eye Center, Second Affiliated Hospital, School of Medicine, Zhejiang University; ; 2. Zhejiang Provincial Key Lab of Ophthalmology, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Yao
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D015687:Cell Hypoxia / Q000502:physiology*; D002460:Cell Line; D002829:Choroid / Q000098:blood supply / Q000166:cytology; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism*; D005786:Gene Expression Regulation; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000166:cytology / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: C571458:MIRN126 microRNA, rat; D035683:MicroRNAs; D042461:Vascular Endothelial Growth Factor A; D020780:Matrix Metalloproteinase 9
keywords: Diabetic retinopathy.; Hypoxia; Matrix metalloproteinase-9; MicroRNA-126; Vascular endothelial growth factor