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 Proxl 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 TpR-l inhibitor accelerated lymphangiogenesis in a mouse model of chronic peritonitis. Lymphangiogenesis was also induced by TβR-l 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.
| Original language | English |
|---|---|
| Pages (from-to) | 4571-4579 |
| Number of pages | 9 |
| Journal | Blood |
| Volume | 111 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - May 1 2008 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Hematology
- Biochemistry
- Cell Biology
- Immunology
Cite this
Inhibition of endogenous TGF-2 signaling enhances lymphangiogenesis. / Oka, Masako; Iwata, Caname; Suzuki, Hiroshi I.; Kiyono, Kunihiko; Morishita, Yasuyuki; Watabe, Tetsuro; Komuro, Akiyoshi; Kano, Mitsunobu; Miyazono, Kohei.
In: Blood, Vol. 111, No. 9, 01.05.2008, p. 4571-4579.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inhibition of endogenous TGF-2 signaling enhances lymphangiogenesis
AU - Oka, Masako
AU - Iwata, Caname
AU - Suzuki, Hiroshi I.
AU - Kiyono, Kunihiko
AU - Morishita, Yasuyuki
AU - Watabe, Tetsuro
AU - Komuro, Akiyoshi
AU - Kano, Mitsunobu
AU - Miyazono, Kohei
PY - 2008/5/1
Y1 - 2008/5/1
N2 - 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 Proxl 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 TpR-l inhibitor accelerated lymphangiogenesis in a mouse model of chronic peritonitis. Lymphangiogenesis was also induced by TβR-l 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.
AB - 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 Proxl 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 TpR-l inhibitor accelerated lymphangiogenesis in a mouse model of chronic peritonitis. Lymphangiogenesis was also induced by TβR-l 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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UR - http://www.scopus.com/inward/citedby.url?scp=47149083462&partnerID=8YFLogxK
U2 - 10.1182/blood-2007-10-120337
DO - 10.1182/blood-2007-10-120337
M3 - Article
C2 - 18310502
AN - SCOPUS:47149083462
VL - 111
SP - 4571
EP - 4579
JO - Blood
JF - Blood
SN - 0006-4971
IS - 9
ER -