Epithelial-mesenchymal interactions are linked to neovascularization.
Lung morphogenesis is dependent on interactions between mesenchymal and epithelial cells. We have previously demonstrated that inhibition of neovascularization by endothelial monocyte-activating polypeptide (EMAP) II also attenuates fetal lung morphogenesis in vivo, and hypothesized that epithelial-mesenchymal interactions are regulated by vascular signals. To address this postulate, we evaluated the formation of epithelial cysts in vitro and assessed this complex interaction through: (i) identification of vascular formation in vitro; (ii) assessment of the effect of selective vascular inhibition on cell viability, proliferation, and cellular interactions as measured by epithelial cyst formation; and (iii) examination of whether there is an interdependent relationship between epithelial and mesenchymal cells and a vascular mediator's protein expression. Vascular networks in vitro formed in direct relationship to the presence of epithelial cysts. Disruption of the vasculature by delivery of a selective antiangiogenic protein EMAP II was associated with disruption of epithelial cyst formation. Lastly, control of the vascular formation regulatory protein EMAP II is a direct result of epithelial-mesenchymal cell interactions. These findings suggest that vascular formation modulates and is modulated by the normal cellular communication and interactions that direct lung morphology.
Schwarz
Margaret A
MA
Department of Pediatrics, Childrens Hospital Los Angeles Research Institute, Los Angeles Center for Craniofacial Molecular Biology, California, USA. m.schwarz@umdnj.edu
Wan
ZeSheng
Z
Liu
Jie
J
Lee
Matthew K
MK
D020533:Angiogenesis Inhibitors / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002455:Cell Division; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D008168:Lung / Q000033:anatomy & histology / Q000196:embryology*; D008648:Mesoderm / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009024:Morphogenesis / Q000502:physiology*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D011247:Pregnancy; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D020533:Angiogenesis Inhibitors; D016207:Cytokines; D005353:Fibronectins; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins; C077219:small inducible cytokine subfamily E, member 1