Regulation of trophoblast migration and survival by a novel neural regeneration peptide

REPRODUCTIVE BIOMEDICINE ONLINE

卷:21

Article

Singh, Ambika T.^1,2  Keelan, Jeffrey A.²  Sieg, Frank^1,2 

[1] Neuren Pharmaceut Ltd, Auckland, New Zealand

[2] Univ Auckland, Liggins Inst, Auckland 1, New Zealand

关键词: NRP;    placenta;    trophoblast migration;    trophoblast survival;   

DOI  :  10.1016/j.rbmo.2010.04.004

来源: Elsevier

【 摘 要 】

Although placental trophoblast migration is tightly controlled in an autocrine/paracrine manner, the nature of chemoattractive factors facilitating and directing this biological activity remains largely elusive. Neural regeneration peptides (NRP), a recently discovered peptide family, stimulate neuronal migration, differentiation and survival of post-natal neurons within the murine central nervous system. Based on the neural-repair related activities of these peptides and parallels between neuronal and placental cell behaviour patterns, this study postulated that they play a role in placental development, in particular trophoblast migration and survival and investigated the role of a newly discovered NRP motif (NNZ-4920), which exhibits about 70% homology to the mouse NRP motif sequence and is homologous to a 13-mer fragment within the N-terminus of human CAPS2, in trophoblast migration and survival regulation. NNZ-4920 significantly enhanced trophoblast migration by 51% (P < 0.01) compared with controls and protected against stress induced by serum withdrawal and tumour necrosis factor-alpha/interferon-gamma treatment, at femtomolar concentrations, with efficacy similar to epidermal growth factor. CAPS2 expression was detected in purified term trophoblast and decidual cells. In conclusion, the placenta may be a source of NRP-related gene expression. Its encoded peptide products exert biological effects on term trophoblast migration and survival in vitro. (C) 2010, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

【 授权许可】

Free