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Oncotarget. 2017 Mar 7;8(10):17347-17359. doi: 10.18632/oncotarget.14468.

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.

Author information

1
Department of Neurosurgery, The First Hospital of Jilin University, Changchun, P.R. China.
2
Department of Ophthalmology, The First Hospital of Jilin University, Changchun, P.R. China.
3
Department of Radiology, The First Hospital of Jilin University, Changchun, P.R. China.

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.

CONCLUSION:

Overexpressed lncRNA ANRIL upregulates VEGF and promotes angiogenesis by activating NF-κB signaling pathway in DM + CI rats. .

KEYWORDS:

NF-κB signaling pathway; cerebral infarction; diabetes mellitus; lncRNA ANRIL; vascular endothelial growth factor

PMID:
28060742
PMCID:
PMC5370045
DOI:
10.18632/oncotarget.14468
[Indexed for MEDLINE]
Free PMC Article

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