High glucose and/or high insulin affects HIF-1 signaling by regulating AIP1 in human umbilical vein endothelial cells

Li, Shuang; Qin, Li; Yu, Wenlin; Xiao, Qiang

doi:10.1016/j.diabres.2015.05.005

Cited by 12 publications

(12 citation statements)

References 33 publications

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“…47 Similarly, increased HIF-1α and VEGF were observed upon DAB2IP KO in human endothelial cells. 48 Finally, DAB2IP ablation was shown to induce Once phosphorylated, IκB undergoes polyubiquitination and degradation, releasing p65/p50 NF-κB from its inhibitory binding, and leading to transcriptional activation. 84,85 Ligand-bound TNFR1 can also catalyze formation of a multiprotein complex that recruits and activates ASK1 (apoptosis signal-regulating kinase), leading to activation of the pro-apoptotic JNK and p38 MAP kinases.…”

Section: Dab2ip Inactivation Fosters Tumor Progressionmentioning

confidence: 99%

Block one, unleash a hundred. Mechanisms of DAB2IP inactivation in cancer

2016

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One of the most defining features of cancer is aberrant cell communication; therefore, a molecular understanding of the intricate network established among tumor cells and their microenvironment could significantly improve comprehension and clinical management of cancer. The tumor suppressor DAB2IP (Disabled homolog 2 interacting protein), also known as AIP1 (ASK1 interacting protein), has an important role in this context, as it modulates signal transduction by multiple inflammatory cytokines and growth factors. DAB2IP is a Ras-GAP, and negatively controls Ras-dependent mitogenic signals. In addition, acting as a signaling adaptor, DAB2IP modulates other key oncogenic pathways, including TNFα/NF-κB, WNT/β-catenin, PI3K/AKT, and androgen receptors. Therefore, DAB2IP inactivation can provide a selective advantage to tumors initiated by a variety of driver mutations. In line with this role, DAB2IP expression is frequently impaired by methylation in cancer. Interestingly, recent studies reveal that tumor cells can employ other sophisticated mechanisms to disable DAB2IP at the post-transcriptional level. We review the mechanisms and consequences of DAB2IP inactivation in cancer, with the purpose to support and improve research aimed to counteract such mechanisms. We suggest that DAB2IP reactivation in cancer cells could be a strategy to coordinately dampen multiple oncogenic pathways, potentially limiting progression of a wide spectrum of tumors.

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Section: Dab2ip Inactivation Fosters Tumor Progressionmentioning

confidence: 99%

Block one, unleash a hundred. Mechanisms of DAB2IP inactivation in cancer

2016

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“…In the cell culture, cells were supplemented with another 100 nmol/L insulin for high insulin treatment. HUVECS were divided into three groups: high insulin group: HUVECS supplemented with 100 nmol/L insulin (Sigma) for 24 h (Li et al 2015a). 3-MA + high insulin group: 3-methyladenine (3-MA, 10 mM, Sigma) was added 30 min before HUVEC incubation with insulin (Chen et al 2017), and the control group was cultured in parallel over 24 h without 3-MA or insulin (Chen et al 2017).…”

Section: Human Umbilical Vein Endothelial Cells (Huvecs)mentioning

confidence: 99%

Hyperinsulinemia restrains endometrial angiogenesis during decidualization in early pregnancy

Chen

Yang

et al. 2019

Journal of Endocrinology

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Previous research on the role of insulin has focused on metabolism. This study investigated the effect of insulin on angiogenesis in endometrial decidualization. High insulin-treated mouse model was constructed by subcutaneous injection of insulin. Venous blood glucose, serum insulin, P4, E2, FSH and LH levels in the pregnant mice were detected by ELISA. Decidual markers, angiogenesis factors and decidual vascular network were detected during decidualization in the pregnant mouse model and an artificially induced decidualization mouse model. Tube formation ability and angiogenesis factors expression were also detected in high insulin-treated HUVECS cells. To confirm whether autophagy participates in hyperinsulinemia-impaired decidual angiogenesis, autophagy was detected in vivo and in vitro. During decidualization, in the condition of high insulin, serum insulin and blood glucose were significantly higher, while ovarian steroid hormones were also disordered (P < 0.05), decidual markers BMP2 and PRL were significantly lower (P < 0.05). Uterine CD34 staining showed that the size of the vascular sinus was significantly smaller than that in control. Endometrial VEGFA was significantly decreased after treatment with high insulin in vivo and in vitro (P < 0.05), whereas ANG-1 and TIE2 expression was significantly increased (P < 0.05). In addition, aberrant expression of autophagy markers revealed that autophagy participates in endometrial angiogenesis during decidualization (P < 0.05). After treatment with the autophagy inhibitor 3-MA in HUVEC, the originally damaged cell tube formation ability and VEGFA expression were repaired. This study suggests that endometrial angiogenesis during decidualization was impaired by hyperinsulinemia in early pregnant mice.

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“…Under hypoxic conditions, the low availability of oxygen inhibits the activity of hydroxylase, which stabilizes the HIF-α subunits (1). Besides the hypoxic microenvironment, HIF-1α and HIF-2α are also affected by many other factors, such as viral hepatitis infections, the glucose metabolism, proto-oncogenes, and mutated tumor suppressor genes (3)(4)(5)(6). It has been reported that both hepatitis B and C viruses can stabilize the HIF-1α protein and promote a pseudohypoxic state (1,3,7).…”

Section: Introductionmentioning

confidence: 99%

Hepatitis B virus induces hypoxia-inducible factor-2α expression through hepatitis B virus X protein

Liu

Yang

et al. 2015

Oncology Reports

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A growing number of studies suggest that the hepatitis B virus X protein (HBx) enhances the protein stability of the hypoxia-inducible factor-1α (HIF-1α). However, the relationship between hepatitis B virus (HBV), HBx and hypoxia-inducible factor-2α (HIF-2α) has not yet been fully elucidated. Immunohistochemical analysis was employed to detect the expression of HIF-2α in normal liver, HBV-related chronic hepatitis, and HBV-related and non-HBV-related hepatocellular carcinoma (HCC) tissues. Quantitative real‑time PCR (qPCR) and western blotting were used to investigate the impact of HBV and HBx on the expression of HIF‑2α. Immunoprecipitation and immunofluorescence were applied to explore the underlying mechanisms. The HIF‑2α expression was found to be higher in HBV‑related chronic hepatitis tissues than in normal liver tissues. Furthermore, it was higher in HBV‑related HCC tissues and HBV‑integrated HepG2 cells than in the corresponding non‑HBV‑related HCC tissues and HepG2 cells. Both HBV and HBx enhanced the protein stability of HIF‑2α. HBx‑mediated upregulation of HIF‑2α resulted mainly from an inhibition of the degradation of HIF‑2α due to the binding of HBx to the von Hippel‑Lindau protein (pVHL). In addition, HBx upregulated the expression of HIF‑2α by activating the NF‑κB signaling pathway. Thus, the present study identified that HBV induces the HIF‑2α expression through its encoded protein HBx. This upregulates the HIF-2α expression by binding to the pVHL activating the NF-κB signaling pathway.

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High glucose and/or high insulin affects HIF-1 signaling by regulating AIP1 in human umbilical vein endothelial cells

Cited by 12 publications

References 33 publications

Block one, unleash a hundred. Mechanisms of DAB2IP inactivation in cancer

Block one, unleash a hundred. Mechanisms of DAB2IP inactivation in cancer

Hyperinsulinemia restrains endometrial angiogenesis during decidualization in early pregnancy

Hepatitis B virus induces hypoxia-inducible factor-2α expression through hepatitis B virus X protein

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