Possible action of vasohibin-1 as an inhibitor in the regulation of vascularization of the bovine corpus luteum

Shirasuna, Koumei; Kobayashi, Akito; Nitta, Akane; Nibuno, Sayo; Sasahara, Kiemi; Shimizu, Takashi; Bollwein, Heinrich; Miyamoto, Akio

doi:10.1530/rep-11-0465

Cited by 16 publications

(5 citation statements)

References 43 publications

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“…VASH1 and VASH2 were discovered as a VEGF‐induced antiangiogenic factor (Shibuya et al., ; Watanabe et al., ). Recombinant VASH1 completely inhibited network formation by EC in vitro as well as angiogenesis in vivo (Shirasuna et al., ; Watanabe et al., ). These findings are supported by our previous studies, in which the expression of VEGF in small follicle was low and in preovulatory follicles just before ovulation was acutely upregulated (Berisha et al., ).…”

Section: Discussionmentioning

confidence: 99%

“…HIF1A has been demonstrated to have critical roles in angiogenesis via transcriptional regulation of angiogenic factor, such as VEGF (Krock, Skuli, & Simon, ; Nishimura & Okuda, ). Vasohibin‐1 (VASH1) as a member of vasohibin system was recently discovered as a novel endothelium‐derived inhibitor of ovarian vascularization (Shirasuna et al., ). The expression of VASH1 was described for bovine CL and it was suggested to play a critical role in ovarian angiogenesis as a novel negative feedback regulator, which inhibits VEGF‐based angiogenesis (Shimizu et al., ; Shirasuna et al., ; Watanabe et al., ).…”

Section: Introductionmentioning

confidence: 99%

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Expression pattern of HIF1alpha and vasohibins during follicle maturation and corpus luteum function in the bovine ovary

Berisha

Schams

Rodler

et al. 2016

Reprod Domestic Animals

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The aim of this study was to characterize expression patterns of hypoxia-inducible factor-1alpha (HIF1A) and vasohibin family members (VASH1 and VASH2) during different stages of ovarian function in cow. Experiment 1: Antral follicle classification occurred by follicle size and estradiol-17beta (E2) concentration in the follicular fluid into 5 groups (<0.5, 0.5-5, 5-40, 40-180 and >180 E2 ng/ml). Experiment 2: Corpora lutea (CL) were assigned to the following stages: days 1-2, 3-4, 5-7, 8-12, 13-16 and >18 (after regression) of oestrous cycle and of pregnancy (months 1-2, 3-4, 6-7, >8). Experiment 3: Cows on days 8-12 were injected with a prostaglandin F2alpha (PGF) analogue and CL were collected before and 0.5, 2, 4, 12, 24, 48 and 64 hr after PGF injection. Expression of mRNA was measured by qPCR, steroid hormone concentration by EIA and localization by immunohistochemistry. HIF1A mRNA expression in our study increases significantly in follicles during final maturation. The highest HIF1A mRNA expression was detected during the early luteal phase, followed by a significant decrease afterwards. In contrast, the mRNA of vasohibins in small follicle was high, followed by a continuous and significant downregulation in preovulatory follicles. The obtained results show a remarkable inverse expression and localization pattern of HIF1A and vasohibins during different stages of ovarian function in cow. These results lead to the assumption that the examined factors are involved in the local mechanisms regulating angiogenesis and that the interactions between proangiogenic (HIF1A) and antiangiogenic (vasohibins) factors impact all stages of bovine ovary function.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Expression pattern of HIF1alpha and vasohibins during follicle maturation and corpus luteum function in the bovine ovary

Berisha

Schams

Rodler

et al. 2016

Reprod Domestic Animals

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“…The concept of negative feedback regulation of VEGF emerged from the discovery of vasohibins (VASHs)[39] and led to the hypothesis that VASH-1 is a negative regulator of VEGF's angiogenic action in the corpus luteum [40]. Also, the discovery that the delta-like ligand 4 (DLL4) -Notch receptor system negatively regulates VEGF-mediated angiogenesis, led to experiments by Fraser and colleagues demonstrating that DLL4 neutralization during luteal development increased angiogenesis but markedly suppressed the progestogenic function and lifespan of the primate corpus luteum [41].…”

Section: Angiogenesis and Luteal Structure-functionmentioning

confidence: 99%

Endocrine and local control of the primate corpus luteum

Stouffer

Bishop

Bogan

et al. 2013

Reproductive Biology

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The primate corpus luteum is a transient endocrine gland that differentiates from the ovulatory follicle midway through the ovarian (menstrual) cycle. Its formation and limited lifespan is critical for fertility, as luteal-derived progesterone is the essential steroid hormone required for embryo implantation and maintenance of intra-uterine pregnancy until the placenta develops. It is well-established that LH and the LH-like hormone, CG, are the vital luteotropic hormones during the menstrual cycle and early pregnancy, respectively. Recent advances, particularly through genome analyses and cellular studies, increased our understanding of various local factors and cellular processes associated with the development, maintenance and repression of the corpus luteum. These include paracrine or autocrine factors associated with angiogenesis (e.g., VEGF), and that mediate LH/CG actions (e.g., progesterone), or counteract luteotropic effects (i.e., local luteolysis; e.g., PGF2α). However, areas of mystery and controversy remain, particularly regarding the signals and events that initiate luteal regression in the non-fecund cycle. Novel approaches capable of gene “knockdown” or amplification”, in vivo as well as in vitro, should identify novel or underappreciated gene products that are regulated by or modulate LH/CG actions to control the functional lifespan of the primate corpus luteum. Further advances in our understanding of luteal physiology will help to improve or control fertility for purposes ranging from preservation of endangered primate species to designing novel ovary-based contraceptives and treating ovarian disorders in women. R01 HD020869, R01 HD042000, U54 HD018185, U54 HD055744, P51 OD011092, T32 HD007133, Bayer Schering Pharma AG.

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“…VEGF is found to induce VASH1 expression in human umbilical vein endothelial cells (HUVECs) (6) similarly to fibroblast growth factor 2 (FGF-2) (7,8). VASH1 was identified to be an intrinsic and specific feedback inhibitor playing an important role in activating ECs engaged in angiogenesis (7,9,10), while exogenous VASH1 hindered sprouting angiogenesis by solid tumors (11,12). In recent studies, it was found that, expression of VASH1 is…”

Section: Introductionmentioning

confidence: 99%

Generation and characterization of rabbit polyclonal antibodies against Vasohibin-2 for determination of its intracellular localization

Sun

Han

et al. 2013

International Journal of Oncology

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Vasohibin-2 was recently identified as an important pro-angiogenesis factor in solid tumor and intracellular localization of its variants is important for elucidating the downstream mechanism(s) of its effects. Currently there are no reported antibodies affordable for intracellular localization. The aim of this study was to generate and characterize polyclonal antibodies against Vasohibin-2 and to determine the intracellular localization of Vasohibin-2. In this study, two polypeptides were synthesized and one prokaryotic Vasohibin-2 recombinant protein was custom-made. New Zealand rabbits were immunized with the polypeptide mixture and prokaryotic recombinant protein, respectively. The purified antibodies from the antiserum were validated by ELISA, western blotting (WB), immunofluorescence (IF), immunohistochemistry (IHC) and immunoprecipitation (IP). In order to determine intracellular localization, the cytoplasmic and nuclear proteins of the human liver cancer cell line HepG2 were isolated for the detection of Vasohibin-2 by western blotting. Vasohibin-2 cDNA, coding for 311 and 355 amino acid residues, fused with or without a DDK/V5 tag at the c-terminus, respectively, was cloned into the Lv-CMV-EGFP vector. Lentiviruses were successfully packaged. Vasohibin-2-overexpressing HepG2-VASH2 (355 amino acid residues) and HepG2-VASH2-V5 (311 amino acid residues fused with V5 tag at the c-terminus) human liver cancer cell lines were established. Approximately 1-2x106 HepG2, HepG2-VASH2 and HepG2-VASH2-V5 cells were injected subcutaneously into the flanks of BALB/c nude mice. Xenograft tumors were harvested for immunohistochemistry. HepG2 cells were transiently transfected with the Lv-CMV-EGFP vectors containing Vasohibin-2 cDNA (coding for 311/355 amino acid residues with a DDK tag at the c-terminal), followed by anti-DDK immunofluorescence. The antibodies obtained were able to detect human VASH2 successfully as applied in western blotting, IF, IHC and IP. Results from IF, IHC and WB (post cytoplasmic/nuclear protein isolation) showed a quite different intracellular localization of VASH2 protein. The VASH2 (with 355 amino acid residues) was located in the cytoplasm while VASH2 (with 311 amino acid residues) was located in the nucleus. The former was found to be a relatively low abundance protein. We successfully generated three rabbit anti-human Vasohibin-2 polyclonal antibodies which can be used for western blotting, IF, IP and IHC. These antibodies will provide a convenient tool for further studies on Vasohibin-2. This is the first study to report differences in the intracellular localization of the VASH2 protein and, hence, a new research direction on the study of VASH2.

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Possible action of vasohibin-1 as an inhibitor in the regulation of vascularization of the bovine corpus luteum

Cited by 16 publications

References 43 publications

Expression pattern of HIF1alpha and vasohibins during follicle maturation and corpus luteum function in the bovine ovary

Expression pattern of HIF1alpha and vasohibins during follicle maturation and corpus luteum function in the bovine ovary

Endocrine and local control of the primate corpus luteum

Generation and characterization of rabbit polyclonal antibodies against Vasohibin-2 for determination of its intracellular localization

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