In:
Blood, American Society of Hematology, Vol. 111, No. 9 ( 2008-05-01), p. 4571-4579
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0006-4971
,
1528-0020
DOI:
10.1182/blood-2007-10-120337
Language:
English
Publisher:
American Society of Hematology
Publication Date:
2008
detail.hit.zdb_id:
1468538-3
detail.hit.zdb_id:
80069-7
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