Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.
Peptides. 2011 Dec;32(12):2474-83. doi: 10.1016/j.peptides.2011.10.010. Epub 2011 Oct 12.
Apelin and its receptor APJ constitute a signaling pathway best recognized as an important regulator of cardiovascular homeostasis. This multifunctional peptidergic system is currently being described to be involved in embryonic events which extend into vascular, ocular and heart development. Additionally, it is highly expressed in pulmonary tissue. Therefore, the aim of this study was to investigate the role of apelinergic system during fetal lung development. Immunohistochemistry and Western blot analysis were used to characterize apelin and APJ expression levels and cellular localization in normal fetal rat lungs, at five different gestational ages as well as in the adult. Fetal rat lung explants were cultured in vitro with increasing doses of apelin. Treated lung explants were morphometrically analyzed and assessed for MAPK signaling modifications. Both components of the apelinergic system are constitutively expressed in the developing lung, with APJ exhibiting monomeric, dimeric and oligomeric forms in the pulmonary tissue. Pulmonary epithelium also displayed constitutive nuclear localization of the receptor. Fetal apelin expression is higher than adult expression. Apelin supplementation inhibitory effect on branching morphogenesis was associated with a dose dependent decrease in p38 and JNK phosphorylation. The results presented provide the first evidence of the presence of an apelinergic system operating in the developing lung. Our findings also suggest that apelin inhibits fetal lung growth by suppressing p38 and JNK signaling pathways.
Apelin 和其受体 APJ 构成了一个信号通路，被认为是心血管稳态的重要调节因子。这个多功能肽系统目前被描述为参与胚胎事件，这些事件延伸到血管、眼部和心脏的发育。此外，它在肺组织中高度表达。因此，本研究旨在探讨 Apelin 能系统在胎儿肺发育中的作用。免疫组织化学和 Western blot 分析用于研究在五个不同的胎龄以及成年大鼠肺组织中 Apelin 和 APJ 的表达水平和细胞定位。将胎鼠肺组织在体外与不同剂量的 Apelin 一起培养。对处理后的肺组织进行形态计量学分析，并评估 MAPK 信号转导的变化。Apelin 能系统的两个组成部分在发育中的肺中持续表达，APJ 在肺组织中表现出单体、二聚体和寡聚体形式。肺上皮细胞也显示出受体的核内定位。胎儿 Apelin 的表达高于成年表达。Apelin 的补充抑制了分支形态发生，这与 p38 和 JNK 磷酸化的剂量依赖性降低有关。目前的研究结果首次提供了 Apelin 能系统在发育中的肺中起作用的证据。我们的研究结果还表明，Apelin 通过抑制 p38 和 JNK 信号通路来抑制胎儿肺的生长。
