Inhibition of endogenous TGF-2 signaling enhances lymphangiogenesis

Masako Oka, Caname Iwata, Hiroshi I. Suzuki, Kunihiko Kiyono, Yasuyuki Morishita, Tetsuro Watabe, Akiyoshi Komuro, Mitsunobu R. Kano, Kohei Miyazono

Research output: Contribution to journalArticle

146 Citations (Scopus)

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 languageEnglish
Pages (from-to)4571-4579
Number of pages9
JournalBlood
Volume111
Issue number9
DOIs
Publication statusPublished - May 1 2008
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Oka, M., Iwata, C., Suzuki, H. I., Kiyono, K., Morishita, Y., Watabe, T., Komuro, A., Kano, M. R., & Miyazono, K. (2008). Inhibition of endogenous TGF-2 signaling enhances lymphangiogenesis. Blood, 111(9), 4571-4579. https://doi.org/10.1182/blood-2007-10-120337