The apelinergic system in the developing lung: expression and signaling.
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.
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.
Paulina
P
Piairo
Rute S
RS
Moura
Cristina
C
Nogueira-Silva
Jorge
J
Correia-Pinto
D000367:Age Factors; D000818:Animals; D000073861:Apelin; D000075244:Apelin Receptors; D015153:Blotting, Western; D002467:Cell Nucleus / Q000737:chemistry; D004622:Embryo, Mammalian / Q000737:chemistry / Q000196:embryology; D047108:Embryonic Development; D004847:Epithelial Cells / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D005260:Female; D005865:Gestational Age; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000494:pharmacology; D008168:Lung / Q000737:chemistry* / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000254:growth & development; D020935:MAP Kinase Signaling System; D009024:Morphogenesis; D010766:Phosphorylation; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry*; D046509:Tissue Culture Techniques
D000073861:Apelin; D000075244:Apelin Receptors; C498579:Apln protein, rat; C491284:Aplnr protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; C495199:apelin-13 peptide