title: Leukemia inhibitory factor in rat fetal lung development: expression and functional studies.
abstract: BACKGROUND
  Leukemia inhibitory factor (LIF) and interleukin-6 (IL-6) are members of the family of the glycoprotein 130 (gp130)-type cytokines. These cytokines share gp130 as a common signal transducer, which explains why they show some functional redundancy. Recently, it was demonstrated that IL-6 promotes fetal lung branching. Additionally, LIF has been implicated in developmental processes of some branching organs. Thus, in this study LIF expression pattern and its effects on fetal rat lung morphogenesis were assessed.
  
  
  RESULTS
  LIF and its subunit receptor LIFRα expression levels were evaluated by immunohistochemistry and western blot in fetal rat lungs of different gestational ages, ranging from 13.5 to 21.5 days post-conception. Throughout all gestational ages studied, LIF was constitutively expressed in pulmonary epithelium, whereas LIFRα was first mainly expressed in the mesenchyme, but after pseudoglandular stage it was also observed in epithelial cells. These results point to a LIF epithelium-mesenchyme cross-talk, which is known to be important for lung branching process. Regarding functional studies, fetal lung explants were cultured with increasing doses of LIF or LIF neutralizing antibodies during 4 days. MAPK, AKT, and STAT3 phosphorylation in the treated lung explants was analyzed. LIF supplementation significantly inhibited lung growth in spite of an increase in p44/42 phosphorylation. On the other hand, LIF inhibition significantly stimulated lung growth via p38 and Akt pathways.
  
  
  CONCLUSIONS
  The present study describes that LIF and its subunit receptor LIFRα are constitutively expressed during fetal lung development and that they have an inhibitory physiological role on fetal lung branching.
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.
authors.forename: Cristina
authors.initials: C
authors.lastname: Nogueira-Silva
authors.forename: Paulina
authors.initials: P
authors.lastname: Piairo
authors.forename: Emanuel
authors.initials: E
authors.lastname: Carvalho-Dias
authors.forename: Francisca O
authors.initials: FO
authors.lastname: Peixoto
authors.forename: Rute S
authors.initials: RS
authors.lastname: Moura
authors.forename: Jorge
authors.initials: J
authors.lastname: Correia-Pinto
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005333:Fetus / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D053605:Leukemia Inhibitory Factor / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D008168:Lung / Q000196:embryology* / Q000378:metabolism*; D009924:Organ Culture Techniques; D038081:Organogenesis / Q000235:genetics / Q000502:physiology; D011247:Pregnancy; D011650:Pulmonary Alveoli / Q000196:embryology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit