Interplay of neuropilin-1 and semaphorin 3A after partial hepatectomy in rats

Fu, Ling; Kitamura, Tsuneo; Iwabuchi, Kazuhisa; Ichinose, Syozo; Yanagida, Mitsuaki; Ogawa, Hideoki; Watanabe, Sumio; Maruyama, Toshihide; Suyama, Masafumi; Takamori, Kenji

doi:10.3748/wjg.v18.i36.5034

Cited by 7 publications

(5 citation statements)

References 27 publications

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“…Our EC-specific results of NRP1 are in agreement with IHC previously reported 9,10 . NRP1 is typically found in arteries, not veins, during development 32 ; yet in the adult liver, NRP1 is expressed on arteries, veins, and capillaries 9 .…”

Section: Discussionsupporting

confidence: 92%

“…sNrp1 is expected to bind and sequester not only VEGF but also other Nrp1 ligands including PlGF, VEGF-B, and SEMA3A. PlGF, an angiogenic ligand, is upregulated after PHx 42 ; whereas SEMA3A, an anti-angiogenic ligand, is significantly downregulated during the first 6 days following PHx 10 .…”

Section: Discussionmentioning

confidence: 99%

“…Sinusoidal EC of the liver express VEGFR1 and VEGFR2; and genetic ablation of VEGFR2 or inhibition of VEGFR2 activity with tyrosine kinase inhibitors impairs liver regeneration 7,8 . Human liver expresses NRP1 mRNA 5 ; and recently, NRP1 protein was detected on human and rat liver EC 9,10 . In contrast, the liver does not express Nrp2 11 .…”

Section: Introductionmentioning

confidence: 99%

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Regulation of soluble neuropilin 1, an endogenous angiogenesis inhibitor, in liver development and regeneration

et al. 2014

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Summary Neuropilin-1 (NRP1) is a receptor for vascular endothelial growth factor (VEGF). A soluble isoform of Nrp1 (sNrp1) has not been described in the mouse. Our goal was to examine the expression of mouse sNrp1 during liver development and regeneration. sNrp1 was cloned from mouse liver. The expression of sNrp1 and VEGF was examined in mouse liver during postnatal development and regeneration using northern blot, western blot, in situ hybridization, and immunohistochemical analyses. HGF/NRP1 binding was examined in vitro. A novel 588-amino acid sNrp1 isoform was found to contain the ligand binding regions of Nrp1. The adult liver expressed more sNrp1 than full-length Nrp1. In vivo, hepatocytes constitutively expressed VEGF and sNrp1 in the quiescent state. sNrp1 was highly upregulated at P20, a time point coinciding with a plateau in liver and body weights. Following hepatectomy, endogenous levels of sNrp1 decreased during the rapid growth phase; and VEGF levels were highest just prior to and during the angiogenic phase. sNrp1 levels again rose 5-10 days post-hepatectomy, presumably to control regeneration. HGF protein bound NRP1 and binding was competed with sNRP1. We cloned a novel mouse sNrp1 isoform from liver and provide evidence that this endogenous angiogenesis inhibitor may regulate VEGF or HGF bioavailability during normal physiological growth and development as well as during liver regeneration.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

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Regulation of soluble neuropilin 1, an endogenous angiogenesis inhibitor, in liver development and regeneration

et al. 2014

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“…The process of axon guidance in liver regeneration may be mediated by secreted third class semaphorins (Sema3A-G), which bind to a membrane receptor complex whose main component is a transmembrane glycoprotein neuropillin 1 or neuropillin 2, or a heterodimer of the two ( 39 ). The interaction between the semaphorins 3A and neuropillin 1 is also notable in the angiogenic processes ( 40 ). The present study revealed increased expression of neuropillin 1 and neuropillin 2 in the group without application of stem cells between day 0 and 9.…”

Section: Discussionmentioning

confidence: 99%

Liver regeneration during the associating liver partition and portal vein ligation for staged hepatectomy procedure in Susï¿½scrofa is positively modulated by stem cells

et al. 2018

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This present study investigated the impact of the application of stem cells to liver regeneration following the first stage of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). The experiment was conducted on a pig model (n=6, 3 that did not receive application of stem cells, 3 that received application stem cells). Collected samples of liver (day 0 and 9 following surgery) were subjected to complete transcriptome sequencing. In total, 39 differentially expressed genes were found in the group without the application of the stem cells (genes of unwanted processes such as fibrosis and inflammation). In the group that did receive application of stem cells, no significantly differentially expressed genes were found, indicating a properly regenerated liver remnant. The present study therefore demonstrated, to the best of our knowledge for the first time, the positive effect of stem cells application in the liver regeneration process during ALPPS procedure in the pig model.

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“…Interestingly, specimens obtained at the reoperation showed positive immunoreactivity. Similarly, NRP-1 is constitutively expressed in sinusoidal endothelial cells in normal liver, but its expression increases following resection of liver for sinusoidal remodeling (29). NRP-1 expression can be stimulated in response to tissue injury or hypoxic conditions (30,31).…”

Section: Discussionmentioning

confidence: 99%

NRP-1 expression is strongly associated with the progression of pituitary adenomas

Lee

Yoo

et al. 2014

Oncology Reports

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The purpose of the present study was to identify a predictive marker associated with tumor progression or recurrence. We investigated the expression of p53, Ki-67, Bax, Bcl-2, vascular endothelial growth factor (VEGF)-A, VEGFR-1, VEGFR-2 and neuropilin-1 (NRP-1) in pituitary adenomas (PAs) with/without tumor progression during follow-up periods. We compared the expression of these molecules in primary and recurrent specimens to identify a predictive marker associated with tumor progression. Nineteen patients had no progression for more than 5-years of follow-up. Nine patients had tumor progression within 5 years of their first transsphenoidal surgery (TSS) surgery and underwent re-TSS for treating progression of adenoma. Tumor size was larger and involvement of the cavernous sinus was more frequent in the progression group than these variables in the no progression group. A strong association was observed between NRP-1 expression and tumor progression. No significant risk for developing tumor progression was associated with Ki-67, p53, Bax, Bcl-2, VEGFR-1, VEGFR-2, or VEGF-A expression. Four of nine patients showed strong NRP-1 immunoreactivity in progression specimens. Negative NRP-1 immunoreactivity in the initial specimens was converted into strong positivity in the progression specimens of five patients. NRP-1 could be a relevant PA marker of progression and could be a potential target for medical therapy.

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Interplay of neuropilin-1 and semaphorin 3A after partial hepatectomy in rats

Abstract: The interplay of Nrp-1 and Sema3A shown in our results may lead to a better understanding of interaction between sinusoidal remodeling and SECs during liver regeneration.

Cited by 7 publications

References 27 publications

Regulation of soluble neuropilin 1, an endogenous angiogenesis inhibitor, in liver development and regeneration

Regulation of soluble neuropilin 1, an endogenous angiogenesis inhibitor, in liver development and regeneration

Liver regeneration during the associating liver partition and portal vein ligation for staged hepatectomy procedure in Susï¿½scrofa is positively modulated by stem cells

NRP-1 expression is strongly associated with the progression of pituitary adenomas

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