Bone morphogenetic protein-9 inhibits lymphatic vessel formation via activin receptor-like kinase 1 during development and cancer progression

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Bone morphogenetic protein-9 inhibits lymphatic vessel formation via activin receptor-like kinase 1 during development and cancer progression. / Yoshimatsu, Yasuhiro; Lee, Yulia G.; Akatsu, Yuichi; Taguchi, Luna; Suzuki, Hiroshi I.; Cunha, Sara I.; Maruyama, Kazuichi; Suzuki, Yuka; Yamazaki, Tomoko; Katsura, Akihiro; Oh, S. Paul; Zimmers, Teresa A.; Lee, Se-Jin; Pietras, Kristian; Koh, Gou Young; Miyazono, Kohei; Watabe, Tetsuro.

In: Proceedings of the National Academy of Sciences, Vol. 110, No. 47, 2013, p. 18940-18945.

Research output: Contribution to journalArticle

Harvard

Yoshimatsu, Y, Lee, YG, Akatsu, Y, Taguchi, L, Suzuki, HI, Cunha, SI, Maruyama, K, Suzuki, Y, Yamazaki, T, Katsura, A, Oh, SP, Zimmers, TA, Lee, S-J, Pietras, K, Koh, GY, Miyazono, K & Watabe, T 2013, 'Bone morphogenetic protein-9 inhibits lymphatic vessel formation via activin receptor-like kinase 1 during development and cancer progression', Proceedings of the National Academy of Sciences, vol. 110, no. 47, pp. 18940-18945. https://doi.org/10.1073/pnas.1310479110

APA

CBE

Yoshimatsu Y, Lee YG, Akatsu Y, Taguchi L, Suzuki HI, Cunha SI, Maruyama K, Suzuki Y, Yamazaki T, Katsura A, Oh SP, Zimmers TA, Lee S-J, Pietras K, Koh GY, Miyazono K, Watabe T. 2013. Bone morphogenetic protein-9 inhibits lymphatic vessel formation via activin receptor-like kinase 1 during development and cancer progression. Proceedings of the National Academy of Sciences. 110(47):18940-18945. https://doi.org/10.1073/pnas.1310479110

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Author

Yoshimatsu, Yasuhiro ; Lee, Yulia G. ; Akatsu, Yuichi ; Taguchi, Luna ; Suzuki, Hiroshi I. ; Cunha, Sara I. ; Maruyama, Kazuichi ; Suzuki, Yuka ; Yamazaki, Tomoko ; Katsura, Akihiro ; Oh, S. Paul ; Zimmers, Teresa A. ; Lee, Se-Jin ; Pietras, Kristian ; Koh, Gou Young ; Miyazono, Kohei ; Watabe, Tetsuro. / Bone morphogenetic protein-9 inhibits lymphatic vessel formation via activin receptor-like kinase 1 during development and cancer progression. In: Proceedings of the National Academy of Sciences. 2013 ; Vol. 110, No. 47. pp. 18940-18945.

RIS

TY - JOUR

T1 - Bone morphogenetic protein-9 inhibits lymphatic vessel formation via activin receptor-like kinase 1 during development and cancer progression

AU - Yoshimatsu, Yasuhiro

AU - Lee, Yulia G.

AU - Akatsu, Yuichi

AU - Taguchi, Luna

AU - Suzuki, Hiroshi I.

AU - Cunha, Sara I.

AU - Maruyama, Kazuichi

AU - Suzuki, Yuka

AU - Yamazaki, Tomoko

AU - Katsura, Akihiro

AU - Oh, S. Paul

AU - Zimmers, Teresa A.

AU - Lee, Se-Jin

AU - Pietras, Kristian

AU - Koh, Gou Young

AU - Miyazono, Kohei

AU - Watabe, Tetsuro

N1 - The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Molecular Medicine (013031200)

PY - 2013

Y1 - 2013

N2 - Lymphatic vessels (LVs) play critical roles in the maintenance of fluid homeostasis and in pathological conditions, including cancer metastasis. Although mutations in ALK1, a member of the transforming growth factor (TGF)-beta/bone morphogenetic protein (BMP) receptor family, have been linked to hereditary hemorrhagic telangiectasia, a human vascular disease, the roles of activin receptor-like kinase 1(ALK-1) signals in LV formation largely remain to be elucidated. We show that ALK-1 signals inhibit LV formation, and LVs were enlarged in multiple organs in Alk1-depleted mice. These inhibitory effects of ALK-1 signaling were mediated by BMP-9, which decreased the number of cultured lymphatic endothelial cells. Bmp9-deficient mouse embryos consistently exhibited enlarged dermal LVs. BMP-9 also inhibited LV formation during inflammation and tumorigenesis. BMP-9 downregulated the expression of the transcription factor prospero-related homeobox 1, which is necessary to maintain lymphatic endothelial cell identity. Furthermore, silencing prospero-related homeobox 1 expression inhibited lymphatic endothelial cell proliferation. Our findings reveal a unique molecular basis for the physiological and pathological roles of BMP-9/ALK-1 signals in LV formation.

AB - Lymphatic vessels (LVs) play critical roles in the maintenance of fluid homeostasis and in pathological conditions, including cancer metastasis. Although mutations in ALK1, a member of the transforming growth factor (TGF)-beta/bone morphogenetic protein (BMP) receptor family, have been linked to hereditary hemorrhagic telangiectasia, a human vascular disease, the roles of activin receptor-like kinase 1(ALK-1) signals in LV formation largely remain to be elucidated. We show that ALK-1 signals inhibit LV formation, and LVs were enlarged in multiple organs in Alk1-depleted mice. These inhibitory effects of ALK-1 signaling were mediated by BMP-9, which decreased the number of cultured lymphatic endothelial cells. Bmp9-deficient mouse embryos consistently exhibited enlarged dermal LVs. BMP-9 also inhibited LV formation during inflammation and tumorigenesis. BMP-9 downregulated the expression of the transcription factor prospero-related homeobox 1, which is necessary to maintain lymphatic endothelial cell identity. Furthermore, silencing prospero-related homeobox 1 expression inhibited lymphatic endothelial cell proliferation. Our findings reveal a unique molecular basis for the physiological and pathological roles of BMP-9/ALK-1 signals in LV formation.

KW - lymphangiogenesis

KW - angiogenesis

KW - blood vascular endothelial cells

U2 - 10.1073/pnas.1310479110

DO - 10.1073/pnas.1310479110

M3 - Article

VL - 110

SP - 18940

EP - 18945

JO - Proceedings of the National Academy of Sciences

JF - Proceedings of the National Academy of Sciences

SN - 1091-6490

IS - 47

ER -