Abstract
BackgroundLeukemia 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.Methodology/Principal FindingsLIF 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/SignificanceThe 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.
Highlights
Fetal lung development is a complex process, involving several effectors such as growth factors, extracellular matrix interactions, hormones and as, recently described inflammatory mediators [1,2,3]
Conclusions/Significance: The present study describes that Leukemia inhibitory factor (LIF) and its subunit receptor LIF receptor alpha subunit (LIFRa) are constitutively expressed during fetal lung development and that they have an inhibitory physiological role on fetal lung branching
It was already demonstrated that interleukin-6 (IL-6) promotes fetal lung maturation [4,5,6] and that IL-6 is constitutively expressed in pulmonary primitive epithelium and enhances fetal lung branching [3]
Summary
Fetal lung development is a complex process, involving several effectors such as growth factors, extracellular matrix interactions, hormones and as, recently described inflammatory mediators [1,2,3]. This family comprises IL-6, leukemia inhibitory factor (LIF), IL-11, oncostatin M, ciliary neurotrophic factor (CNTF), cardiotropin-1 (CT-1) and cardiotrophin-like cytokine These cytokines share the membrane glycoprotein gp130 as a common signal transducer which explains the fact that these show some functional redundancy even though they exhibit specific biological activities [7,8]. Several studies have emphasized the importance of LIF signaling in several processes of branching organs This cytokine inhibits fetal nephrons formation [14,15,16], induces mammary gland involution [17], decreases thyroid tumors growth [18,19] and increases pancreatic regeneration [20]. 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. In this study LIF expression pattern and its effects on fetal rat lung morphogenesis were assessed
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
