Neuromedin B induces angiogenesis via activation of ERK and Akt in endothelial cells

Park, Hyun-Joo; Kim, Su-Ryun; Bae, Soo-Kyung; Choi, Yoon Kyung; Bae, Yun Jung; Kim, Eok-Cheon; Kim, Woo Jean; Jang, Hye-Ock; Yun, Il Dong; Kim, Young‐Myeong; Bae, Moon‐Kyoung

doi:10.1016/j.yexcr.2009.08.009

Cited by 24 publications

(24 citation statements)

References 31 publications

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“…It secretes the angiogenic peptide hormone, neuromedin B [17,18]; and its angiogenic response involves high expression level of COX proteins [19-21]. The CL13 mouse cell line is also tumorigenic and can induce angiogenic response, thus allowing us to quantify the assay's response in relation to cell lines with different angiogenic potentials [22,23].…”

Section: Resultsmentioning

confidence: 99%

Discriminating Different Cancer Cells Using a Zebrafish in Vivo Assay

Moshal

Ferri-Lagneau

Haider

et al. 2011

Cancers

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Despite the expanded understanding of tumor angiogenesis phenomenon and how it impacts cancer treatment outcomes, we have yet to develop a robust assay that can quickly, easily, and quantitatively measure tumor-induced angiogenesis. Since the zebrafish/tumor xenograft represents an emerging tool in this regard, the present study strives to capitalize on the ease, effectiveness, and the adaptability of this model to quantify tumor angiogenesis. In order to test a range of responses, we chose two different tumorigenic cell lines, the human non-small cell lung carcinoma (H1299) and the mouse lung adenocarcinoma (CL13). Non-tumorigenic 3T3-L1 cells served as negative control. The cells were grafted near to the perivitelline space of the zebrafish embryos and the angiogenic response was analyzed using whole-mount alkaline phosphatase (AP) vessel staining and fluorescence microscopy. Angiogenic activity was scored based on the length and number of the newly formed ectopic vessels and the percentage of embryos with ectopic vessels. At 2 day-post-implantation, we detected a significant increase in the length and number of ectopic vessels with H1299 cell implantation compared to CL13 cell transplantation, both are higher than 3T3-L1 control. We also observed a significantly higher percentage of embryos with ectopic vessels with H1299 and CL13 transplantation compared to the 3T3-L1 control, but this parameter is not as robust and reliable as measuring the length and number of ectopic vessels. Furthermore, the systemic exposure of zebrafish embryos to an anti-angiogenesis drug (PTK 787, inhibitor of vascular endothelial growth factor receptor tyrosine kinase) inhibited tumor-induced angiogenesis, suggesting that the assay can be used to evaluate anti-angiogenic drugs. This study implicates the feasibility of using zebrafish xenotransplantation to perform quantitative measurement of the angiogenic activity of cancer cells which can be further extended to measure cancer cell metastasis. This assay represents not only the useful test for patient diagnosis, but also has the potential for evaluating anti-cancer drugs treatment.

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Section: Resultsmentioning

confidence: 99%

Discriminating Different Cancer Cells Using a Zebrafish in Vivo Assay

Moshal

Ferri-Lagneau

Haider

et al. 2011

Cancers

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“…30 Although, there are no previous data directly linking neuromedin B to cardiac structure, it is involved in angiogenesis. 31 There are also data linking neuromedin B with PTK2 (Protein Tyrosine Kinase 2) and Ca 2+ levels. 32 Interference of PTK2 mRNA by siRNA reverses load-induced ventricular hypertrophy in mice.…”

Section: Discussionmentioning

confidence: 99%

Four Genetic Loci Influencing Electrocardiographic Indices of Left Ventricular Hypertrophy

Shah

Nelson

Gaunt

et al. 2011

Circ Cardiovasc Genet

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Background Presence of left ventricular hypertrophy on an electrocardiogram (ECG-LVH) is widely assessed clinically and provides prognostic information in some settings. There is evidence for significant heritability of ECG-LVH. We conducted a large-scale gene-centric association analysis of four commonly measured indices of ECG-LVH. Methods and Results We calculated Sokolow-Lyon Index, Cornell Product, 12-lead QRS Voltage Sum and 12-lead QRS Voltage Product in 10,256 individuals from 3 population based cohorts and typed their DNA using a customised gene array (the Illumina HumanCVD BeadChip 50K array) containing 49,094 genetic variants in ~2100 genes of cardiovascular relevance. We followed up promising associations in 11,777 additional individuals. We identified and replicated four loci associated with ECG-LVH indices - 3p22.2 (SCN5A, rs6797133, p=1.22×10−7) with Cornell Product and 12q13.3 (PTGES3, rs2290893, p=3.74×10−8), 15q25.2 (NMB, rs2292462, p=3.23×10−9) and 15q26.3 (IGF1R, rs4966014, p=1.26×10−7) with 12-lead QRS Voltage Sum. The odds ratio of being in the top decile for 12-lead QRS Voltage Sum for those carrying 6 trait-raising alleles at the 12q13.3, 15q25.2 and 15q26.3 loci versus those carrying 0–1 alleles was 1.60 (95% CI: 1.20 – 2.29). Lead SNPs at the 12q13.3 and 15q25.2 loci showed significant eQTL effects in monocytes. Conclusions These findings provide novel insights into the genetic determination of ECG-LVH. The findings could help to improve our understanding of the mechanisms determining this prognostically important trait.

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“…Moreover, native and transfected rat Nmbr exhibit similar binding and signaling characteristics in BALB/3T3 cells [13,]. These results have clearly demonstrated that Nmbr is involved in parturition via a number of signaling pathways in addition to its function in the regulation of the nervous system [33][34][35][36][37].…”

Section: Zhang Et Almentioning

confidence: 92%

Neuromedin B and Its Receptor Influence the Activity of Myometrial Primary Cells In Vitro Through Regulation of Il6 Expression via the Rela/p65 Pathway in Mice1

Zhang

Fei

et al. 2012

Biology of Reproduction

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The neuromedin B receptor (Nmbr) is an important physiological regulator of spontaneous activities and stress responses through different cascades as well as its autocrine and paracrine effects. Previous studies have revealed that neuromedin B (Nmb) and its receptor signal via the Rela (also known as p65)/Il6 pathway in a mouse model of pregnancy. This study investigated the mechanism of Nmbr signaling via the Rela/p65-Il6 pathway and regulation of the concentration of intracellular free calcium ([Ca(2+)](i)) during the onset of labor in primary mouse myometrial cell cultures isolated from mice in term labor. Data demonstrated Nmbr agonist-mediated upregulation of the DNA binding activity of Rela/p65, Il6 expression, and [Ca(2+)](i) in a concentration-dependent manner. Furthermore, a significant correlation was observed between DNA binding activity of Rela/p65 and Il6 expression. Moreover, this up-regulation was blocked by Nmbr and Rela/p65 knockdown, achieved by RNA interference (RNAi) technology. No significant differences were identified in the inhibition of Il6 expression as a result of Nmbr or Rela/p65 knockdown. However, significant differences were observed between the [Ca(2+)](i) in Rela/p65-specific group and that in the Nmbr-specific small interfering RNA (siRNA)-treated groups. These data demonstrated that the Nmb/Nmbr interaction in pregnant myometrial primary cells in vitro predominantly influenced uterine activity through regulation of Il6 expression via the Rela/p65 pathway, although the effects of Nmbr on [Ca(2+)](i) involved several pathways that remain to be elucidated.

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Neuromedin B induces angiogenesis via activation of ERK and Akt in endothelial cells

Cited by 24 publications

References 31 publications

Discriminating Different Cancer Cells Using a Zebrafish in Vivo Assay

Discriminating Different Cancer Cells Using a Zebrafish in Vivo Assay

Four Genetic Loci Influencing Electrocardiographic Indices of Left Ventricular Hypertrophy

Neuromedin B and Its Receptor Influence the Activity of Myometrial Primary Cells In Vitro Through Regulation of Il6 Expression via the Rela/p65 Pathway in Mice1

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