Hepatocellular carcinoma cells promote angiogenesis of HUVEC via the eNAMPT-INSR axis
10.19405/j.cnki.issn1000-1492.2024.12.011
- Author:
Junjie Wu
1
;
Shizhou Li
2
;
Chengming Gao
2
;
Pengbo Cao
2
;
Gangqiao Zhou
3
,
4
Author Information
1. Dept of Life Sciences , Anhui Medical University , Hefei 230032
2. Academy of Military Medical Sciences , Academy of Military Sciences , Beijing 100850
3. Dept of Life Sciences , Anhui Medical University , Hefei 230032
4. Academy of Military Medical Sciences , Academy of Military Sciences , Beijing 100850
- Publication Type:Journal Article
- Keywords:
hepatocellular carcinoma;
nicotinamide phosphoribosyl transferase;
insulin receptor;
angiogenesis
- From:
Acta Universitatis Medicinalis Anhui
2024;59(12):2141-2149
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the function and potential mechanism of hepatocellular carcinoma(HCC) cells-derived extracellular nicotinamide phosphoribosyl transferase(eNAMPT) in the angiogenesis of human umbilical vein endothelial cells(HUVEC).
Methods:The eNAMPT secretion of HCC cells were stimulated by hypoxia treatment and investigated the angiogenesis of HUVEC was investigated by tube formation assays. Transcriptomic RNA sequencing(RNA-seq) analyses of HUVEC under eNAMPT treatment were used to explore the mechanism of the effect of eNAMPT-insulin receptor(INSR) axis on angiogenesis. Western blot was used to detect the effects of eNAMPT-INSR axis on protein expression of HUVEC cells. qRT-PCR was used to detect the influence of eNAMPT-INSR axis on the expression of HUVEC intracellular related target genes.
Results:ELISA and Western blot results showed that the protein level of eNAMPT in the culture supernatant of HCC cells increased significantly after hypoxia stimulation.In vitroangiogenesis assay results showed that eNAMPT significantly increased the nodules number and total length of tubes in HUVEC. The transcriptome sequencing results of HUVEC showed that eNAMPT, as an insulin analogue, participated in the regulation of biological processes such as cell migration and angiogenesis in HUVEC, and might promote angiogenesis by activating insulin-like signaling pathways. Western blot results showed that the eNAMPT-INSR axis affected p-AKT and p-ERK1/2 protein levels in PI3K-AKT and MAPK-ERK1/2 signaling pathways in HUVEC. qRT-PCR results showed that the eNAMPT-INSR axis affected the expression of angiogenesis related target genes MMP2, MMP9 and VEGF in HUVEC.
Conclusion:eNAMPT secreted by HCC cells promotes angiogenesis by binding INSR to activate the PI3K-AKT and MAPK-ERK1/2 signaling pathways.
- Full text:2025022715582793316肝癌细胞通过eNAMPT-...进人脐静脉内皮细胞血管生成_吴俊杰.pdf
