Vasohibin induces prolyl hydroxylase‐mediated degradation of hypoxia‐inducible factor‐1α in human umbilical vein endothelial cells

Kozako, Tomohiro; Matsumoto, Noriko; Kuramoto, Yukako; Sakata, Akira; Motonagare, Rie; Aikawa, Akiyoshi; Imoto, Masumi; Toda, Akihisa; Honda, Shin‐ichiro; Shimeno, Hiroshi; Soeda, Shinji

doi:10.1016/j.febslet.2012.03.007

Cited by 14 publications

(14 citation statements)

References 36 publications

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“…30,31,49 VASH1 induces prolyl hydroxylase-mediated degradation of HIF1α via the induction of prolyl hydroxylase. 50 Expression of VASH1 is low in proliferating endothelial cells at the sprouting front but is high in nonproliferating endothelial cells in newly formed blood vessels that are formed behind the sprouting front, which is where angiogenesis terminates. 51 The presence of VASH1 in endothelial cells is also evident in various cancers, atherosclerotic lesions, age-dependent macular degeneration, diabetic retinopathy, rheumatoid arthritis, and arterial re-endothelialization after denudation.…”

Section: Discussionmentioning

confidence: 99%

Deficiency of the MicroRNA-31–MicroRNA-720 Pathway in the Plasma and Endothelial Progenitor Cells From Patients With Coronary Artery Disease

Wang

Huang

et al. 2014

ATVB

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Objective-Defects in angiogenesis/vasculogenesis or vessel repair are major complications of coronary artery disease (CAD). Endothelial progenitor cells (EPCs) play a fundamental role in postnatal vascular repair and CAD. The role of microRNAs in CAD pathogenesis and their potential as biomarkers remain to be elucidated. Approach and Results-MicroRNA-31 (miR-31) level in both the plasma and EPCs of patients with CAD is found lower.miR-31 regulates EPC activities by targeting FAT atypical cadherin 4 and thromboxane A2 receptor, which show increased expression in CAD EPCs. Overexpressing miR-31 in CAD EPCs rescued their angiogenic and vasculogenic abilities both in vitro and in vivo. When exploring approaches to restore endogenous miR-31, we found that far-infrared treatment enhanced the expression of not only miR-31, but also miR-720 in CAD EPCs. miR-720, which was also decreased in EPCs and the plasma of patients with CAD, stimulated EPC activity by targeting vasohibin 1. The miR720-vasohibin 1 pair was shown to be downstream of FAT atypical cadherin 4, but not of thromboxane A2 receptor. FAT atypical cadherin 4 inhibited miR-720 expression via repression of the planar cell polarity signaling gene four-jointed box 1 (FJX1), which was required for miR-720 expression through a hypoxia-inducible factor 1, α subunit-dependent mechanism. Restoring miR-720 level strengthened activity of CAD EPCs. The miR-31-miR-720 pathway is shown critical to EPC activation and that downregulation of this pathway contributes to CAD pathogenesis. Circulating levels of miR-31, miR-720, and vasohibin 1 have the potential to allow early diagnosis of CAD and to act as prognosis biomarkers for CAD and other EPC-related diseases. In addition to the number of circulating EPCs present, the regulation of postnatal angiogenesis/vasculogenesis also depends on the activity of mobilized EPCs. 8 In addition to the effects of protein-coding genes, the expression of various different microRNAs (miRNAs, miRs) also plays a critical role in the clinical course of CAD. miRNAs are a class of endogenous, small, noncoding, single-stranded RNAs of ≈22 nucleotides in length. The mature miRNAs negatively regulate gene expression by targeting specific mRNAs for cleavage or translational repression. Detecting the levels of tissue miRNAs, as well as the levels of circulating miRNAs in body fluids, is considered to be a potential approach to identifying new disease biomarkers and novel drug targets. Conclusions-Manipulating9-11 Many proangiogenic and antiangiogenic miRNAs have been pinpointed. Examples such as miR-221 and miR-222, which are transcribed from the same miR-221/222 cluster, have been shown to be able to modulate the angiogenic properties of human umbilical vein endothelial cells by targeting c-Kit and endothelial NO synthase.12,13 miR-221/222 levels in EPCs are significantly higher in patients with CAD.14,15 miR-10a* and miR-21 are also known to modulate EPC senescence via the suppression of high-mobility group A2.16 miR-10b and miR-196b, on the cont...

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Section: Discussionmentioning

confidence: 99%

Deficiency of the MicroRNA-31–MicroRNA-720 Pathway in the Plasma and Endothelial Progenitor Cells From Patients With Coronary Artery Disease

Wang

Huang

et al. 2014

ATVB

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“…The results of a study regarding the relationship between the HIF-1α and VASH1 in human umbilical vein endothelial cells (HUVECs) showed that H 2 O 2 -treatments impaired VEGF induced vasohibin expressions, as well as HUVECs growth. Also, the results of another study confirmed that vasohibin elevated prolyl hydroxylase (PHD), which regulates the prolyl hydroxylation of HIF-1α, and resulted in ubiquitin-mediated proteasomal degradation 14 ( Fig. 3 ).…”

Section: Vasohibins Expressions and Their Regulationmentioning

confidence: 63%

The roles of vasohibin and its family members: Beyond angiogenesis modulators

Zhao

Lü

et al. 2017

Cancer Biology & Therapy

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Vasohibin-1 is an intrinsic angiogenesis inhibitor, and is expressed in endothelial cells via induction by pro-angiogenesis factors. It is known to inhibit several processes of angiogenesis, with different mechanisms from extrinsic angiogenesis inhibitors. Vasohibin-2 is mainly expressed by mononuclear cells which have been mobilized from bone marrow. It not only promotes angiogenesis, but also modulates the releases of FGF-2 and VEGF, which are the two major inducers for vasohibin1. Hypoxic environment induces the expression of hypoxia-inducible Factor 1α with a result of VEGF release nearly in all tumor cell lines and tissues. However, it has been observed that hypoxia reduces the inducible effects of VEGF on vasohibin, which indicates that a complicated mechanism exists in the angiogenesis. Vasohibin and its family members play important roles in both the physiological and pathological procedures, in contrary but complementary patterns. Furthermore, human aortic smooth muscle cells and fibroblast have also been detected to express vasohibin on a moderate to weak scale range. Recently, the results of an increasing number of studies in vivo have shown that vasohibin can also be detected in several cancers, and is associated with micro-vessel densities, histology grades, invasions, poor clinical features, metastasis, and dissemination in abdominal cavities, as well as EMT. In more recent reports, it has been confirmed that, along with being angiogenesis regulators, a variety of other roles have been associated with this family. The focus of this study was the upstream regulatory mechanisms of vasohibin expressions, and their role in regard to the downstream target proteins of vasohibin, especially in carcinoma. Vasohibin is considered to be an original angiogenesis inhibitor, and has a much broader significance in pathological processes. It can be taken as an independent prognostic factor, as well as a potential strategy for cancer therapy programs.

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“…An anticancer effect of VASH1 through its inhibition of tumor angiogenesis has been confirmed in several reports [ 96 , 99 , 100 ]. Although this protein was shown to induce prolyl hydroxylase-mediated degradation of hypoxia-inducible factor-1 α [ 101 ], the precise mechanism for its antiangiogenic activity remains to be elucidated. The receptor(s) for VASH1 on endothelial cells and its intracellular signaling pathway have not yet been detected.…”

Section: Vasohibin-1 As a Novel Therapeutic Agentmentioning

confidence: 99%

Antiangiogenic Therapy for Diabetic Nephropathy

Tanabe

Maeshima

Sato

et al. 2017

BioMed Research International

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Angiogenesis has been shown to be a potential therapeutic target for early stages of diabetic nephropathy in a number of animal experiments. Vascular endothelial growth factor (VEGF) is the main mediator for abnormal angiogenesis in diabetic glomeruli. Although beneficial effects of anti-VEGF antibodies have previously been demonstrated in diabetic animal experiments, recent basic and clinical evidence has revealed that the blockade of VEGF signaling resulted in proteinuria and renal thrombotic microangiopathy, suggesting the importance of maintaining normal levels of VEGF in the kidneys. Therefore, antiangiogenic therapy for diabetic nephropathy should eliminate excessive glomerular angiogenic response without accelerating endothelial injury. Some endogenous antiangiogenic factors such as endostatin and tumstatin inhibit overactivation of endothelial cells but do not specifically block VEGF signaling. In addition, the novel endothelium-derived antiangiogenic factor vasohibin-1 enhances stress tolerance and survival of the endothelial cells, while inhibiting excess angiogenesis. These factors have been demonstrated to suppress albuminuria and glomerular alterations in a diabetic mouse model. Thus, antiangiogenic therapy with promising candidates will possibly improve renal prognosis in patients with early stages of diabetic nephropathy.

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Vasohibin induces prolyl hydroxylase‐mediated degradation of hypoxia‐inducible factor‐1α in human umbilical vein endothelial cells

Cited by 14 publications

References 36 publications

Deficiency of the MicroRNA-31–MicroRNA-720 Pathway in the Plasma and Endothelial Progenitor Cells From Patients With Coronary Artery Disease

Deficiency of the MicroRNA-31–MicroRNA-720 Pathway in the Plasma and Endothelial Progenitor Cells From Patients With Coronary Artery Disease

The roles of vasohibin and its family members: Beyond angiogenesis modulators

Antiangiogenic Therapy for Diabetic Nephropathy

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