Hypoxia-inducible factor 1 upregulation of both VEGF and ANGPTL4 is required to promote the angiogenic phenotype in uveal melanoma

Hu, Ke; Babapoor-Farrokhran, Savalan; Rodrigues, Murilo Wendeborn; Deshpande, Monika; Puchner, Brooks; Kashiwabuchi, Fabiana; Hassan, Syed Junaid; Asnaghi, Laura; Handa, James T.; Merbs, Shannath L.; Eberhart, Charles G.; Semenza, Gregg L.; Montaner, Silvia; Sodhi, Akrit

doi:10.18632/oncotarget.6868

Cited by 100 publications

(70 citation statements)

References 47 publications

(56 reference statements)

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“…Follistatin treatment, through blocking activins or transforming growth factor‐beta superfamily members, reduced renal injury by I/R . The combination of VEGF and HGF or ANGPTL4 was reported to improve angiogenic response of tissues. Moreover, uPAR was also suggested as a crucial factor in VEGF‐mediated endothelial cell migration .…”

Section: Discussionmentioning

confidence: 99%

Controlled Delivery of Stem Cell-Derived Trophic Factors Accelerates Kidney Repair After Renal Ischemia-Reperfusion Injury in Rats

Yim

Kim

Chung

et al. 2019

Stem Cells Translational Medicine

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Renal disease is a worldwide health issue. Besides transplantation, current therapies revolve around dialysis, which only delays disease progression but cannot replace other renal functions, such as synthesizing erythropoietin. To address these limitations, cell‐based approaches have been proposed to restore damaged kidneys as an alternative to current therapies. Recent studies have shown that stem cell‐derived secretomes can enhance tissue regeneration. However, many growth factors undergo rapid degradation when they are injected into the body in a soluble form. Efficient delivery and controlled release of secreting factors at the sites of injury would improve the efficacy in tissue regeneration. Herein, we developed a gel‐based delivery system for controlled delivery of trophic factors in the conditioned medium (CM) secreted from human placental stem cells (HPSCs) and evaluated the effect of trophic factors on renal regeneration. CM treatment significantly enhanced cell proliferation and survival in vitro. Platelet‐rich plasma (PRP) was used as a delivery vehicle for CM. Analysis of the release kinetics demonstrated that CM delivery through the PRP gel resulted in a controlled release of the factors both in vitro and in vivo. In an acute kidney injury model in rats, functional and structural analysis showed that CM delivery using the PRP gel system into the injured kidney minimized renal tissue damage, leading to a more rapid functional recovery when compared with saline, CM, or vehicle only injection groups. These results suggest that controlled delivery of HPSC‐derived trophic factors may provide efficient repair of renal tissue injury. stem cells translational medicine 2019;8:959&970

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Section: Discussionmentioning

confidence: 99%

Controlled Delivery of Stem Cell-Derived Trophic Factors Accelerates Kidney Repair After Renal Ischemia-Reperfusion Injury in Rats

Yim

Kim

Chung

et al. 2019

Stem Cells Translational Medicine

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“…These studies indicated that the up-regulated ANGPTL4 was highly related with the ROS production and podocyte apoptosis. Interestingly, it also has been demonstrated that the expression of ANGPTL4 is HIF-1α dependent [23,24]. Considering all the information mentioned above, we believe the EGCG may attenuate Adriamycin-induced FSGS through the suppression of oxidant stress and podocyte apoptosis by targeting the HIF-1α/ANGPTL4 pathway.…”

Section: Introductionmentioning

confidence: 75%

“…Recently, an increasing number of evidences have indicated the close relationship between HIF-1α and ANG-PTL4 [23,24,37]. ANGPTL4 may play a vital role in FSGS.…”

Section: Discussionmentioning

confidence: 99%

Epigallocatechin-3-Gallate Attenuates Adriamycin-Induced Focal Segmental Glomerulosclerosis via Suppression of Oxidant Stress and Apoptosis by Targeting Hypoxia-Inducible Factor-1α/ Angiopoietin-Like 4 Pathway

Liu¹,

2019

Pharmacology

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Background: Focal and segmental glomerular sclerosis (FSGS) is a common cause of nephrotic syndrome and end-stage renal disease. It has been reported that overproduction of reactive oxygen species (ROS) and cell apoptosis are associated with the development of FSGS. Epigallocatechin-3-gallate (EGCG) is a bioactive constituent accounting for more than 50% of the total catechins in green tea, which have anti-oxidative and anti-apoptotic effects. Based on this, this study was designed to evaluate the renoprotective effect of EGCG treatment on Adriamycin-induced FSGS. Methods: In C57BL/6 mice, Adriamycin nephropathy (AN) was induced by Adriamycin (10 mg/kg body weight, diluted in normal saline) via a tail vein on day 0. Then the mice were given with EGCG (20 mg/kg body weight) or YC-1 (Lificiguat, a specific inhibitor of hypoxia-inducible factor-1α [HIF-1α], 50 mg/kg body weight) or both intraperitoneally. Both the EGCG and YC-1 were given on the day of Adriamycin injection and continued for 6 weeks. The animals were organized into the following 5 groups for the animal experiments: the control group, the AN group, the AN + EGCG group, the AN + YC-1 group and the AN + EGCG + YC-1 group. At 6 weeks, the mice were sacrificed; kidneys and blood samples were collected for further analysis. The HIF-1α and the angiopoietin-like 4 (ANGPTL4) expression were detected by Western blot, real-time PCR, immunohistochemistry or immunofluorescence. Dihydroethidium staining and NADPH oxidase 1 (Nox1) measurement were used to detect ROS production. Terminal deoxynucleotide transferase-mediated dUTP nick end-labeling (TUNEL) staining and caspase-3 measurement was used to detect cell apoptosis. Results: When the animals were treated with Adriamycin, both the ROS production and TUNEL positive cells increased. Besides, the expression of HIF-1α, ANGPTL4, and caspase-3 were also up-regulated, while EGCG treatment could attenuate these changes. Interestingly, compared with treatment with YC-1 or EGCG alone, more pronounced inhibition of ANGPTL4, caspase-3 and Nox1 were obtained when YC-1 and EGCG were administered simultaneously. Conclusion: EGCG attenuates FSGS through the suppression of Oxidant Stress and apoptosis by targeting the HIF-1α/ANGPTL4 pathway.

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“…VEGF is a glycosylated multifunctional protein. VEGF level has been shown to correlate well with angiopoiesis of several types of tumors (15). VEGF is the first angiogenesis factor ever found to be induced by hypoxic condition, and a significant target gene among those directly regulated by HIF-1.…”

Section: Discussionmentioning

confidence: 99%

Correlation between liver cancer pain and the HIF-1 and VEGF expression levels

et al. 2016

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A possible correlation between liver cancer pain and the hypoxia-inducible factor (HIF)-1 and vascular endothelial growth factor (VEGF) expression levels was examined. From January, 2015 to January, 2016, 30 patients suffering from liver cancer with pain, 30 patients with liver cancer without pain and 30 hepatitis patients with pain were enrolled in the study. Pain level was evaluated by visual analogue scale (VAS), the expression levels of HIF-1 and VEGF mRNA were determined by RT-PCR and the expression levels of HIF-1 and VEGF proteins were examined by ELISA. Before intervention, the VAS in the hepatitis group was significantly higher than that of the liver cancer pain group. However, after intervention the VAS in the two groups was reduced. HIF-1 and VEGF mRNA expression levels in the liver cancer pain group were significantly higher than those in the liver cancer group before and after intervention. The expression levels of HIF-1 and VEGF mRNA in the hepatitis group were the lowest. The expression levels of HIF-1 and VEGF mRNA in the liver cancer pain group considerably increased after intervention. The expression levels of HIF-1 and VEGF mRNA in the other two groups showed no changes before or after intervention. Before and after the intervention, VAS in the liver cancer pain group was positively correlated to the expression levels of HIF-1 and VEGF. Thus, pain occurrence and the pain level in liver cancer patients were correlated with the expression levels of HIF-1 and VEGF. As the regular three-step medicine analgesic ladder is ineffective in these cases, verification of HIF-1 and VEGF expression levels may be considered the new target for pain release.

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Hypoxia-inducible factor 1 upregulation of both VEGF and ANGPTL4 is required to promote the angiogenic phenotype in uveal melanoma

Cited by 100 publications

References 47 publications

Controlled Delivery of Stem Cell-Derived Trophic Factors Accelerates Kidney Repair After Renal Ischemia-Reperfusion Injury in Rats

Controlled Delivery of Stem Cell-Derived Trophic Factors Accelerates Kidney Repair After Renal Ischemia-Reperfusion Injury in Rats

Epigallocatechin-3-Gallate Attenuates Adriamycin-Induced Focal Segmental Glomerulosclerosis via Suppression of Oxidant Stress and Apoptosis by Targeting Hypoxia-Inducible Factor-1α/ Angiopoietin-Like 4 Pathway

Correlation between liver cancer pain and the HIF-1 and VEGF expression levels

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