TY - JOUR
T1 - Epithelial-mesenchymal interactions are linked to neovascularization
AU - Schwarz, Margaret A.
AU - Wan, ZeSheng
AU - Liu, Jie
AU - Lee, Matthew K.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2004/6
Y1 - 2004/6
N2 - 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.
AB - 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.
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U2 - 10.1165/rcmb.2003-0145OC
DO - 10.1165/rcmb.2003-0145OC
M3 - Article
C2 - 14672913
AN - SCOPUS:2942521198
VL - 30
SP - 784
EP - 792
JO - American Journal of Respiratory Cell and Molecular Biology
JF - American Journal of Respiratory Cell and Molecular Biology
SN - 1044-1549
IS - 6
ER -