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Inhibition of endogenous TGF-β signaling enhances lymphangiogenesis
Lymphangiogenesis is induced by various growth factors, including VEGF-C. Although TGF-β plays crucial roles in angiogenesis, the roles of TGF-β signaling in lymphangiogenesis are unknown. We show here that TGF-β transduced signals in human dermal lymphatic microvascular endothelial cells (HDLECs) a...
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Published in: | Blood 2008-05, Vol.111 (9), p.4571-4579 |
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Main Authors: | , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Lymphangiogenesis is induced by various growth factors, including VEGF-C. Although TGF-β plays crucial roles in angiogenesis, the roles of TGF-β signaling in lymphangiogenesis are unknown. We show here that TGF-β transduced signals in human dermal lymphatic microvascular endothelial cells (HDLECs) and inhibited the proliferation, cord formation, and migration toward VEGF-C of HDLECs. Expression of lymphatic endothelial cell (LEC) markers, including LYVE-1 and Prox1 in HDLECs, as well as early lymph vessel development in mouse embryonic stem cells in the presence of VEGF-A and C, were repressed by TGF-β but were induced by TGF-β type I receptor (TβR-I) inhibitor. Moreover, inhibition of endogenous TGF-β signaling by TβR-I inhibitor accelerated lymphangiogenesis in a mouse model of chronic peritonitis. Lymphangiogenesis was also induced by TβR-I inhibitor in the presence of VEGF-C in pancreatic adenocarcinoma xenograft models inoculated in nude mice. These findings suggest that TGF-β transduces signals in LECs and plays an important role in the regulation of lymphangiogenesis in vivo. |
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ISSN: | 0006-4971 1528-0020 |
DOI: | 10.1182/blood-2007-10-120337 |