Preliminary Research of Main Components of Dll4/ Notch -VEGF Signaling Pathway Under High-Glucose Stimulation In Vitro

Abstract Background Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes. Celastrol plays a certain role in the improvement of various diabetes complications. Therefore, this study aimed to explore whether celastrol inhibited the proliferation and angiogenesis of high glucose (HG)-induced human retinal endothelial cells (hRECs) by down-regulating the HIF1/VEGF signaling pathway. Methods The viability and proliferation of hRECs treated with glucose, celastrol or dimethyloxallyl glycine (DMOG) were analyzed by MTT assay. The invasion and tube formation ability of hRECs treated with glucose, celastrol or DMOG were in turn detected by transwell assay and tube formation assay. The expression of HIF1α and VEGF in hRECs after indicated treatment was analyzed by Western blot analysis and RT-qPCR analysis and ICAM-1 expression in hRECs after indicated treatment was detected by immunofluorescence assay Results HG induction promoted the proliferation, invasion and tube formation ability and increased the expression of HIF-1α and VEGF of hRECs, which were gradually suppressed by celastrol changing from 0.5 to 2.0 μM. DMOG was regarded as a HIF1α agonist, which attenuated the effect of celastrol on HG-induced hRECs. Conclusion Celastrol inhibited the proliferation and angiogenesis of HG-induced hRECs by down-regulating the HIF1α/VEGF signaling pathway.

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Spatholobus suberectus extract suppresses proliferation and EMT, and promotes apoptosis in palmitic acid induced vascular endothelial cells by inhibiting LncRNA MALAT1 via VEGF signaling pathway

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v19i5.6 ◽

2020 ◽

Vol 19 (5) ◽

pp. 494-955

Author(s):

Kebo Gu ◽

Lili He

Keyword(s):

Palmitic Acid ◽

Signaling Pathway ◽

Vascular Endothelial Cell ◽

Vascular Endothelial ◽

Mesenchymal Transition ◽

Vegf Signaling ◽

Lncrna Malat1 ◽

Spatholobus Suberectus ◽

Vegf Signaling Pathway

Purpose: In type 2 diabetes, palmitic acid could damage vessels and induce insulin resistance. This present in vitro study evaluates the possible role of Spatholobus suberectus (FSS) extract in diabetes.Methods: Human HUVECc cells were treated with palmitic acid, palmitic acid and Spatholobus suberectus extract. MALAT1 overexpression plasmid (pcDNA-MALAT1) and blank vector were transfected into the cells using lipofectamine 2000. RT-qPCR assay was used to evaluated the expression changes of lncRNA, VEGFR2 and VEGFA in the cells as well as Epithelial-Mesenchymal Transition (EMT) biomarkers and apoptosis. CCK-8 was used to detect cell viabilities of HUVECs. Expressions of proteins in VEGF signaling pathway were analyzed using Western Blot.Results: LncRNA MALAT1 had high expression in diabetes-like cells and suppressed proliferation and EMT but promoted apoptosis. The SS extract promoted proliferation and EMT and repressed apoptosis in diabetes-like HUVECs cells. The promotion of apoptosis by LncRNA MALAT1, inhibition of apoptosis and regulated functions of diabetes-like HUVECs cells by SS extract occurred via the VEGF signaling pathwayConclusion: SS extract might contribute to survival of cells by inhibiting MALAT1 via VEGF signaling pathway in vitro, suggesting FSF might be a potential therapeutic agent in the treatment of diabetes. Keywords: flavone of Spatholobus suberectus, diabetes, vascular endothelial cell, LncRNA MALAT1

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RAB42 Promotes Glioma Pathogenesis via the VEGF Signaling Pathway

Frontiers in Oncology ◽

10.3389/fonc.2021.657029 ◽

2021 ◽

Vol 11 ◽

Author(s):

Baoling Liu ◽

Quanping Su ◽

Bolian Xiao ◽

Guodong Zheng ◽

Lizhong Zhang ◽

...

Keyword(s):

Signaling Pathways ◽

Signaling Pathway ◽

Molecular Mechanisms ◽

Killer Cell ◽

Gene Set Enrichment Analysis ◽

Signal Pathways ◽

Vegf Signaling ◽

Gene Functions ◽

Vegf Signaling Pathway

Angiogenesis plays an important role in tumor initiation and progression of glioma. Seeking for biomarkers associated with angiogenesis is important in enhancing our understanding of glioma biologically and identifying its new drug targets. RNA-sequencing (RNA-seq) data and matched clinical data were downloaded from the CGGA database. A series of filtering analyses were performed to screen for reliable genes: survival, multivariate Cox, ROC curve filtration, and clinical correlation analyses. After immunohistochemical verification, RAB42 was identified as a reliable gene for further single gene analysis. Afterwards, we performed gene set enrichment analysis (GSEA) and co-expression analysis to establish the related molecular mechanisms and signal pathways in glioma. Finally, the gene functions and the mechanisms were investigated in vitro experiments. A total of 23270 mRNA expression and 1018 glioma samples were included in this study. After the three filtering analyses, we selected ten genes for immunohistochemical verification: KLHDC8A, IKIP, HIST1H2BK, HIST1H2BJ, GNG5, FAM114A1, TMEM71, RAB42, CCDC18, and GAS2L3. Immunostaining demonstrated that RAB42 was significantly expressed on the membrane of glioma tissues but not in normal tissues. These results were verified and validated in GEPIA datasets, and the association between RAB42 with clinical features was also evaluated. Analysis of gene functions indicated that RAB42 activated VEGF signaling pathways and the mechanism was associated with natural killer cell mediated cytotoxicity, JAK-STAT signaling pathway and apoptosis pathways by PI3K/AKT in gliomas. Experiments in vitro suggested that the proliferation and invasion of glioma cells might be inhibited after downregulating of RAB42. And the tumorigenesis promotion of RAB42 may relate to the activation of VEGF signaling pathway. Taken together, this study shows that the overexpression of RAB42 is an independent prognostic factor of adverse prognosis. Its pro-oncogenic mechanism may be associated with the activation of VEGF signaling pathways.

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