Bone morphogenetic protein-9 inhibits lymphatic vessel formation via activin receptor-like kinase 1 during development and cancer progression
(2013) In Proceedings of the National Academy of Sciences 110(47). p.18940-18945- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4196644
- author
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- lymphangiogenesis, angiogenesis, blood vascular endothelial cells
- in
- Proceedings of the National Academy of Sciences
- volume
- 110
- issue
- 47
- pages
- 18940 - 18945
- publisher
- National Academy of Sciences
- external identifiers
-
- wos:000327100600059
- scopus:84888084861
- pmid:24133138
- ISSN
- 1091-6490
- DOI
- 10.1073/pnas.1310479110
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Molecular Medicine (013031200)
- id
- 4d7f4c99-319c-4aea-84cc-9b3303a3f0bb (old id 4196644)
- date added to LUP
- 2016-04-01 10:56:55
- date last changed
- 2022-04-28 03:08:39
@article{4d7f4c99-319c-4aea-84cc-9b3303a3f0bb, abstract = {{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.}}, author = {{Yoshimatsu, Yasuhiro and Lee, Yulia G. and Akatsu, Yuichi and Taguchi, Luna and Suzuki, Hiroshi I. and Cunha, Sara I. and Maruyama, Kazuichi and Suzuki, Yuka and Yamazaki, Tomoko and Katsura, Akihiro and Oh, S. Paul and Zimmers, Teresa A. and Lee, Se-Jin and Pietras, Kristian and Koh, Gou Young and Miyazono, Kohei and Watabe, Tetsuro}}, issn = {{1091-6490}}, keywords = {{lymphangiogenesis; angiogenesis; blood vascular endothelial cells}}, language = {{eng}}, number = {{47}}, pages = {{18940--18945}}, publisher = {{National Academy of Sciences}}, series = {{Proceedings of the National Academy of Sciences}}, title = {{Bone morphogenetic protein-9 inhibits lymphatic vessel formation via activin receptor-like kinase 1 during development and cancer progression}}, url = {{http://dx.doi.org/10.1073/pnas.1310479110}}, doi = {{10.1073/pnas.1310479110}}, volume = {{110}}, year = {{2013}}, }