Isolation of a small vasohibin-binding protein (SVBP) and its role in vasohibin secretion

Suzuki, Yasuhiro; Kobayashi, Masako; Miyashita, Hiroki; Ohta, Hiroyuki; Sonoda, Hidenori; Sato, Yasufumi

doi:10.1242/jcs.067538

Cited by 57 publications

(66 citation statements)

References 48 publications

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“…Here, we showed that CM from human VASH2 transfectants stimulated the migration of endothelial cells. Ovarian cancer cells express SVBP, a secretory chaperone of vasohibins (15). These results suggest that VASH2 is secreted from the cancer cells and acts on neighboring endothelial cells to stimulate angiogenesis in a paracrine manner.…”

Section: Discussionmentioning

confidence: 83%

“…The amino acid sequence of the human VASH2 protein is 52.5% homologous to that of human VASH1, and both VASH1 and VASH2 are highly conserved among species. VASH1 and VASH2 lack the classical signal sequence; but they bind to the small intracellular vasohibin-binding protein (SVBP), and this binding with SVBP facilitates their secretion (15). Because of the similarity between VASH1 and VASH2, we examined their expression and function by the use of hypoxia-induced subcutaneous angiogenesis in mice.…”

Section: Introductionmentioning

confidence: 99%

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Vasohibin-2 Expressed in Human Serous Ovarian Adenocarcinoma Accelerates Tumor Growth by Promoting Angiogenesis

Takahashi

Koyanagi

Suzuki

et al. 2012

Molecular Cancer Research

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106

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Vasohibin-1 (VASH1) is a VEGF-inducible endothelium-derived angiogenesis inhibitor and VASH2 is its homolog. Our previous analysis revealed that VASH1 is expressed in endothelial cells to terminate angiogenesis, whereas VASH2 is expressed in infiltrating mononuclear cells mobilized from bone marrow to promote angiogenesis in a mouse model of hypoxia-induced subcutaneous angiogenesis. To test the possible involvement of VASH2 in the tumor, we examined human ovarian cancer cells for the presence of VASH2. Immunohistochemical analysis revealed that VASH2 protein was preferentially detected in cancer cells of serous ovarian adenocarcinoma. We then used SKOV-3 and DISS, two representative human serous adenocarcinoma cell lines, and examined the role of VASH2 in the tumor. The knockdown of VASH2 showed little effect on the proliferation of cancer cells in vitro but notably inhibited tumor growth, peritoneal dissemination, and tumor angiogenesis in a murine xenograft model. Next, we stably transfected the human VASH2 gene into two types of murine tumor cells, EL-4 and MLTC-1, in which endogenous VASH2 was absent. When either EL-4 or MLTC-1 cells were inoculated into VASH2 (À/À) mice, the VASH2 transfectants formed bigger tumors when compared with the controls, and the tumor microvessel density was significantly increased. VASH2 stimulated the migration of endothelial cells, and its increased expression in cancer cells is related to the decrease of mir-200b. These results indicate that VASH2 expressed in serous ovarian carcinoma cells promoted tumor growth and peritoneal dissemination by promoting angiogenesis. Mol Cancer Res; 10(9); 1135-46. Ó2012 AACR.

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Section: Discussionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Vasohibin-2 Expressed in Human Serous Ovarian Adenocarcinoma Accelerates Tumor Growth by Promoting Angiogenesis

Takahashi

Koyanagi

Suzuki

et al. 2012

Molecular Cancer Research

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106

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“…More recently, the critical role of VASH-1 in the maintenance of endothelial cells against cellular stressors and the regulatory mechanisms of its synthesis via posttranscriptional regulation mediated by the binding of HuR proteins to AU-rich elements in the 3′ untranslated region of VASH-1 mRNAs have been reported [9]. VASH-1 does not contain a classic signal sequence; rather, a small vasohibin-binding protein (SVBP) serves as its secretory chaperon and contributes to its antiangiogenic effects [10]. To date, no cell surface receptors for VASH-1 have been identified.…”

Section: Introductionmentioning

confidence: 99%

Urinary and Plasma Levels of Vasohibin-1 Can Predict Renal Functional Deterioration in Patients with Renal Disorders

et al. 2014

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Vasohibin-1 (VASH-1) is a negative feedback regulator of angiogenesis, and a small vasohibin-binding protein (SVBP) serves as its secretory chaperone and contributes to its antiangiogenic effects. In the present study, we aimed to define the clinical significance of VASH-1 and SVBP in patients with chronic kidney disease (CKD). We recruited 67 Japanese hospitalized patients with renal disorders with (n = 45) or without (n = 22) renal biopsy samples and 10 Japanese healthy controls. We evaluated the correlations between the plasma and urinary levels of VASH-1/VASH-1-SVBP complex/SVBP and the clinicopathological parameters. The plasma levels of VASH-1 were inversely correlated with age and systolic and diastolic blood pressure and positively correlated with crescent formation. Increased plasma and urinary levels of VASH-1 and VASH-1-SVBP complex were significantly correlated with worse renal outcomes. These results demonstrate an association between elevated urinary and plasma levels of VASH-1 and progressive decline of the renal function, thus suggesting a potential role for VASH-1 in predicting a worse renal prognosis in patients with renal disease, including CKD.

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“…In addition, VASH-1 inhibits lymphangiogenesis and lymph node metastasis of tumors (16). VASH-1 does not contain a classic signal sequence, and a small vasohibin-binding protein (SVBP) serves as a secretory chaperon for VASH-1 and contributes to the antiangiogenic effects of VASH-1 (39). To date, cell surface receptors for VASH-1 have not been reported.…”

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confidence: 99%

Amelioration of renal alterations in obese type 2 diabetic mice by vasohibin-1, a negative feedback regulator of angiogenesis

Saito¹,

Maeshima²,

Nasu³

et al. 2011

American Journal of Physiology-Renal Physiology

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The involvement of VEGF-A as well as the therapeutic efficacy of angiogenesis inhibitors in diabetic nephropathy have been reported. We recently reported the therapeutic effects of vasohibin-1 (VASH-1), an endogenous angiogenesis inhibitor, in a type 1 diabetic nephropathy model (Nasu T, Maeshima Y, Kinomura M, Hirokoshi-Kawahara K, Tanabe K, Sugiyama H, Sonoda H, Sato Y, Makino H. Diabetes 58: 2365-2375, 2009). In this study, we investigated the therapeutic efficacy of VASH-1 on renal alterations in obese mice with type 2 diabetes. Diabetic db/db mice received intravenous injections of adenoviral vectors encoding human VASH-1 (AdhVASH-1) and were euthanized 8 wk later. AdhVASH-1 treatment resulted in significant suppression of glomerular hypertrophy, glomerular hyperfiltration, albuminuria, increase in the CD31(+) glomerular endothelial area, F4/80(+) monocyte/macrophage infiltration, the accumulation of type IV collagen, and mesangial matrix. An increase in the renal levels of VEGF-A, VEGFR-2, transforming growth factor (TGF)-β1, and monocyte chemoattractant protein-1 in diabetic animals was significantly suppressed by AdhVASH-1 (immunoblotting). AdhVASH-1 treatment significantly recovered the loss and altered the distribution patterns of nephrin and zonula occludens (ZO)-1 and suppressed the increase in the number of fibroblast-specific protein-1 (FSP-1(+)) and desmin(+) podocytes in diabetic mice. In vitro, recombinant human VASH-1 (rhVASH-1) dose dependently suppressed the upregulation of VEGF induced by high ambient glucose (25 mM) in cultured mouse podocytes. In addition, rhVASH-1 significantly recovered the mRNA levels of nephrin and the protein levels of ZO-1 and P-cadherin and suppressed the increase in protein levels of desmin, FSP-1, Snail, and Slug in podocytes under high-glucose condition. Taken together, these results suggest the potential use of VASH-1 as a novel therapeutic agent in type 2 diabetic nephropathy mediated via antiangiogenic effects and maintenance of podocyte phenotype in association with antiproteinuric effects.

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Isolation of a small vasohibin-binding protein (SVBP) and its role in vasohibin secretion

Cited by 57 publications

References 48 publications

Vasohibin-2 Expressed in Human Serous Ovarian Adenocarcinoma Accelerates Tumor Growth by Promoting Angiogenesis

Vasohibin-2 Expressed in Human Serous Ovarian Adenocarcinoma Accelerates Tumor Growth by Promoting Angiogenesis

Urinary and Plasma Levels of Vasohibin-1 Can Predict Renal Functional Deterioration in Patients with Renal Disorders

Amelioration of renal alterations in obese type 2 diabetic mice by vasohibin-1, a negative feedback regulator of angiogenesis

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