title: Overexpression of lncRNA ANRIL up-regulates VEGF expression and promotes angiogenesis of diabetes mellitus combined with cerebral infarction by activating NF-κB signaling pathway in a rat model.
abstract: OBJECTIVE
  This study aimed to explore the effects of lncRNA ANRIL on vascular endothelial growth factor (VEGF) and angiogenesis in diabetes mellitus (DM) combined with cerebral infarction (CI) through NF-κB signaling pathway.
  
  
  METHODS
  Adult male Wistar rats were randomly divided into control group and DM + CI group, and the DM + CI group were subdivided into Vector, shANRIL, PDTC, pcDNA-ANRIL, and pcDNA-ANRIL + PDTC groups. VEGF and FMS-like tyrosine kinase (FLT-1) expressions were measured by immunohistochemistry and endothelium dependent microvessel density (MVD) was detected by differentiation 31 (CD31) and para-amiuosalicylic acid (PAS) double staining. The qRT-PCR was applied to measure mRNA expressions of VEGF, FLT-1, Kinase insert domain protein receptor (FLK-1) and NF-κB, and Western blotting was conducted to detected expressions of VEGF, NF-κB and p-IκB/IκB.
  
  
  RESULTS
  Compared with the control group, protein expressions of VEGF, NF-κB, p-IκB/IκB, expression of ANRIL, and mRNA expressions of VEGF, FLT-1 and NF-κB were increased in the DM + CI group. Compared with the Vector group, protein expressions of VEGF, NF-κB, p-IκB/IκB, expression of ANRIL, mRNA expressions of VEGF, FLT-1 and NF-κB, and endothelium dependent MVD were increased in the pcDNA-ANRIL group, while decreased in the shANRIL group and PDTC group. Compared with the pcDNA-ANRIL group, protein expressions of VEGF, NF-κB, p-IκB/IκB, expression of ANRIL, mRNA expressions of VEGF, FLT-1 and NF-κB, and endothelium dependent MVD were decreased in the pcDNA-ANRIL + PDTC group.
  
  
  CONCLUSIONS
  Overexpressed lncRNA ANRIL upregulates VEGF and promotes angiogenesis by activating NF-κB signaling pathway in DM + CI rats. .
authors.affiliation: Department of Neurosurgery, The First Hospital of Jilin University, Changchun, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, The First Hospital of Jilin University, Changchun, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Radiology, The First Hospital of Jilin University, Changchun, P.R. China.
authors.forename: Tie-Feng
authors.initials: TF
authors.lastname: Ji
authors.affiliation: Department of Neurosurgery, The First Hospital of Jilin University, Changchun, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Neurosurgery, The First Hospital of Jilin University, Changchun, P.R. China.
authors.forename: Jin-Lu
authors.initials: JL
authors.lastname: Yu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply / Q000378:metabolism; D002544:Cerebral Infarction / Q000235:genetics* / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics*; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
chemical_list: C000621604:ANRIL long non-coding RNA, rat; C561518:CDKN2B antisense RNA, human; D016328:NF-kappa B; D062085:RNA, Long Noncoding; D042461:Vascular Endothelial Growth Factor A; C501164:Flt1 protein, rat; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: NF-κB signaling pathway; cerebral infarction; diabetes mellitus; lncRNA ANRIL; vascular endothelial growth factor