Inhibition of endogenous TGF-2 signaling enhances lymphangiogenesis

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

Research output: Contribution to journalArticle

133 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

Fingerprint

Lymphangiogenesis
Vascular Endothelial Growth Factor C
Endothelial cells
Endothelial Cells
Skin
Stem cells
Heterografts
Vascular Endothelial Growth Factor A
Lymph
Intercellular Signaling Peptides and Proteins
Peritonitis
Nude Mice
Adenocarcinoma
Cell Proliferation

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Oka, M., Iwata, C., Suzuki, H. I., Kiyono, K., Morishita, Y., Watabe, T., ... 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

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 journalArticle

Oka, M, Iwata, C, Suzuki, HI, Kiyono, K, Morishita, Y, Watabe, T, Komuro, A, Kano, M & Miyazono, K 2008, 'Inhibition of endogenous TGF-2 signaling enhances lymphangiogenesis', Blood, vol. 111, no. 9, pp. 4571-4579. https://doi.org/10.1182/blood-2007-10-120337
Oka M, Iwata C, Suzuki HI, Kiyono K, Morishita Y, Watabe T et al. Inhibition of endogenous TGF-2 signaling enhances lymphangiogenesis. Blood. 2008 May 1;111(9):4571-4579. https://doi.org/10.1182/blood-2007-10-120337
Oka, Masako ; Iwata, Caname ; Suzuki, Hiroshi I. ; Kiyono, Kunihiko ; Morishita, Yasuyuki ; Watabe, Tetsuro ; Komuro, Akiyoshi ; Kano, Mitsunobu ; Miyazono, Kohei. / Inhibition of endogenous TGF-2 signaling enhances lymphangiogenesis. In: Blood. 2008 ; Vol. 111, No. 9. pp. 4571-4579.
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