Adrenomedullin 2 Antagonist Infusion to Rats During Midgestation Causes Fetoplacental Growth Restriction Through Apoptosis1

Chauhan, Madhu; Yallampalli, Uma; Reed, Luckey; Yallampalli, Chandra

doi:10.1095/biolreprod.106.053322

Cited by 34 publications

(41 citation statements)

References 35 publications

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“…For example, IMD is required for rat normal fetoplacental growth, (10) functions as a vasodilator and reduces blood pressure in both normal and hypertensive rats.…”

mentioning

confidence: 99%

“…(10,17,18) Relatively little is known about how IMD might influence cancer development. Smith et al (2009) report that IMD stimulated neovascularization of the rat ischemic hindlimb.…”

mentioning

confidence: 99%

“…(9) IMD regulates diverse physiological processes. For example, IMD is required for rat normal fetoplacental growth, (10) functions as a vasodilator and reduces blood pressure in both normal and hypertensive rats. (11) IMD is expressed in every endocrine organ of the hypothalamo-pituitary-adrenal axis together with its receptor, calcitonin receptor-like receptor (CRLR).…”

mentioning

confidence: 99%

“…(16) Significantly, removal of N-terminal and C-terminal regions of IMD yields the IMD antagonist peptide IMD 17-47aa , which has been shown to block biological function of IMD through a receptor-mediated mechanism. (10,17,18) Relatively little is known about how IMD might influence cancer development. Smith et al (2009) report that IMD stimulated neovascularization of the rat ischemic hindlimb.…”

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confidence: 99%

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Intermedin is overexpressed in hepatocellular carcinoma and regulates cell proliferation and survival

et al. 2012

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Angiogenesis is one of the hallmarks of tumor growth and metastasis. Identification of tumor angiogenic factors has been a critical component in understanding cancer biology and treatment. Intermedin (IMD) has been reported to promote angiogenesis in a rat ischemic model and human umbilical vascular endothelial cells. Our study sought to determine the role of IMD in human hepatocellular carcinoma tumor progression. High IMD mRNA expression levels were observed in human hepatocellular carcinoma tumors, even in early stage disease, by real-time RT-PCR. Immunohistochemical analysis of hepatocellular carcinoma clinical samples demonstrated that the tumor regions were significantly more immunoreactive for IMD than adjacent benign liver. Inhibition of IMD expression using RNA interference reduced cell proliferation in SK-Hep-1 and SNU-398 cells. Blockage of IMD signaling using either an antagonist peptide or a neutralizing antibody inhibited growth in a dose-dependent manner with concomitant induction of apoptosis, causing cleavage of caspase-8 and downregulation of Gli1 and Bcl2. Conversely, addition of IMD active peptide increased the phosphorylation level of extracellular signal-regulated kinase. Thus, IMD might play an important role in cell proliferation and survival of hepatocellular carcinoma. Our data suggests that IMD is a potential biomarker and therapeutic target for hepatocellular carcinoma. (Cancer Sci 2012; 103: 1474-1480 H epatocellular carcinoma (HCC) is the fifth most common cancer worldwide, and the third leading cause of cancer death.(1) The majority (>80%) of liver cancers are HCC.Conventional chemotherapy and hormonal therapies have minimal response rates. (3) Therapeutic agents targeting angiogenesis, which is required for tumor growth and metastasis, are currently in development. (4,5) Of the known angiogenic factors, vascular endothelial growth factor (VEGF) is the most potent pro-angiogenic factor and is secreted by nearly all solid cancers.(5) Sorafenib, an inhibitor targeting the VEGF and platelet-derived growth factor receptors, is the standard of care in patients with advanced HCC.(6) Promising novel inhibitors are under investigation.(7) The key to targeting angiogenesis successfully in the future may be to use a combination of multiple inhibitors against multiple targets. Intermedin (IMD, adrenomedullin-2), is a secreted peptide that belongs to the calcitonin/calcitonin gene-related peptide family.(9) IMD regulates diverse physiological processes. For example, IMD is required for rat normal fetoplacental growth, (10) functions as a vasodilator and reduces blood pressure in both normal and hypertensive rats.(11) IMD is expressed in every endocrine organ of the hypothalamo-pituitary-adrenal axis together with its receptor, calcitonin receptor-like receptor (CRLR). (12) The signaling of IMD is mediated by the interaction of CRLR in association with receptor activity modifying protein 3 (RAMP3).(13) IMD is expressed by endothelial cells, smooth muscle cells and cardiomyocytes at a basal leve...

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“…For example, IMD is required for rat normal fetoplacental growth, (10) functions as a vasodilator and reduces blood pressure in both normal and hypertensive rats.…”

mentioning

confidence: 99%

“…(10,17,18) Relatively little is known about how IMD might influence cancer development. Smith et al (2009) report that IMD stimulated neovascularization of the rat ischemic hindlimb.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Intermedin is overexpressed in hepatocellular carcinoma and regulates cell proliferation and survival

et al. 2012

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“…Administration of an AM2 antagonist causes FGR, highlighting the importance of AM2 in a healthy pregnancy (Chauhan et al, 2006). AM2 is expressed by trophoblast cells and stimulates their invasion via the mitogen-activated protein kinase (MAPK) signaling pathway (Chauhan et al, 2011, Havemann et al, 2013.…”

Section: Trophoblast-derived Factors Affect Unk Cell Recruitmentmentioning

confidence: 99%

Uterine natural killer cells as modulators of the maternal-fetal vasculature

Matson¹,

Caron²

2014

Int. J. Dev. Biol.

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Precise and local control of the innate immune system within the placenta is an essential component for achieving a normal and healthy pregnancy. One of the most abundant immune cells of the placenta is a subpopulation of natural killer (NK) cells that profusely populates the uterine decidua during early pregnancy. Uterine NK (uNK) cells and trophoblast cells of the placenta communicate both directly and indirectly to contribute to the critical process of spiral artery remodeling. Here, we discuss recent findings that expand our knowledge of uNK cell-trophoblast cell crosstalk and the important role it plays in the maternal vascular adaptation to pregnancy.

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Calcitonin Gene Related Family Peptides: Importance in Normal Placental and Fetal Development

Yallampalli

Chauhan

Endsley

et al. 2014

Advances in Fetal and Neonatal Physiology

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Synchronized molecular and cellular events occur between the uterus and the implanting embryo to facilitate successful pregnancy outcome. Nevertheless, the molecular signaling network that coordinates strategies for successful decidualization, placentation and fetal growth are not well understood. The discovery of calcitonin/calcitonin gene-related peptides (CT/CGRP) highlighted new signaling mediators in various physiological processes, including reproduction. It is known that CGRP family peptides including CGRP, adrenomedulin and intermedin play regulatory functions during implantation, trophoblast proliferation and invasion, and fetal organogenesis. In addition, all the CGRP family peptides and their receptor components are found to be expressed in decidual, placental and fetal tissues. Additionally, plasma levels of peptides of the CGRP family were found to fluctuate during normal gestation and to induce placental cellular differentiation, proliferation, and critical hormone signaling. Moreover, aberrant signaling of these CGRP family peptides during gestation has been associated with pregnancy disorders. It indicates the existence of a possible regulatory role for these molecules during decidualization and placentation processes, which are known to be particularly vulnerable. In this review, the influence of the CGRP family peptides in these critical processes is explored and discussed.

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Adrenomedullin 2 Antagonist Infusion to Rats During Midgestation Causes Fetoplacental Growth Restriction Through Apoptosis1

Cited by 34 publications

References 35 publications

Intermedin is overexpressed in hepatocellular carcinoma and regulates cell proliferation and survival

Intermedin is overexpressed in hepatocellular carcinoma and regulates cell proliferation and survival

Uterine natural killer cells as modulators of the maternal-fetal vasculature

Calcitonin Gene Related Family Peptides: Importance in Normal Placental and Fetal Development

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