Abstract
ObjectiveThis 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.MethodsAdult 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-I?B/I?B.ResultsCompared with the control group, protein expressions of VEGF, NF-κB, p-I?B/I?B, 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-I?B/I?B, 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-I?B/I?B, expression of ANRIL, mRNA expressions of VEGF, FLT-1 and NF-κB, and endothelium dependent MVD were decreased in the pcDNA-ANRIL + PDTC group.ConclusionOverexpressed lncRNA ANRIL upregulates VEGF and promotes angiogenesis by activating NF-κB signaling pathway in DM + CI rats.
Highlights
Diabetes mellitus (DM) is characterized by complicated metabolic disorders and has been considered as an common chronic disease in the world, with an incidence approximate to 382 million in 2013, which is classified to be two types including type 1 DM (T1DM) and type 2 DM (T2DM) [1]
DM played an independent role of increasing the risk of cerebral infarction (CI) [2], where CI might be induced by serious metabolic dysfunction [3]
The common initial manifestation of CI might be caused by arterial occlusion, and there is a high mortality of patients when CI combined with T2DM, where the major pathology of CI is thrombosis [4]
Summary
Diabetes mellitus (DM) is characterized by complicated metabolic disorders and has been considered as an common chronic disease in the world, with an incidence approximate to 382 million in 2013, which is classified to be two types including type 1 DM (T1DM) and type 2 DM (T2DM) [1]. DM played an independent role of increasing the risk of cerebral infarction (CI) [2], where CI might be induced by serious metabolic dysfunction [3]. The common initial manifestation of CI might be caused by arterial occlusion, and there is a high mortality of patients when CI combined with T2DM, where the major pathology of CI is thrombosis [4]. CI was stated to be developed with DM by its hypercoagulable state but www.impactjournals.com/oncotarget Primers. Primer sequences (5' - 3') VEGF upstream
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