The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
FOXC2 and fluid shear stress stabilize postnatal lymphatic vasculature
Open accessAbstract
Biomechanical forces, such as fluid shear stress, govern multiple aspects of endothelial cell biology. In blood vessels, disturbed flow is associated with vascular diseases, such as atherosclerosis, and promotes endothelial cell proliferation and apoptosis. Here, we identified an important role for disturbed flow in lymphatic vessels, in which it cooperates with the transcription factor FOXC2 to ensure lifelong stability of the lymphatic vasculature. In cultured lymphatic endothelial cells, FOXC2 inactivation conferred abnormal shear stress sensing, promoting junction disassembly and entry into the cell cycle. Loss of FOXC2-dependent quiescence was mediated by the Hippo pathway transcriptional coactivator TAZ and, ultimately, led to cell death. In murine models, inducible deletion of Foxc2 within the lymphatic vasculature led to cell-cell junction defects, regression of valves, and focal vascular lumen collapse, which triggered generalized lymphatic vascular dysfunction and lethality. Together, our work describes a fundamental mechanism by which FOXC2 and oscillatory shear stress maintain lymphatic endothelial cell quiescence through intercellular junction and cytoskeleton stabilization and provides an essential link between biomechanical forces and endothelial cell identity that is necessary for postnatal vessel homeostasis. As FOXC2 is mutated in lymphedema-distichiasis syndrome, our data also underscore the role of impaired mechanotransduction in the pathology of this hereditary human disease.
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Cites
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Self-citationIntegrin-α9 Is Required for Fibronectin Matrix Assembly during Lymphatic Valve Morphogenesis
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Cited by
Mechanisms of Hippo pathway regulation
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Meningeal lymphatic vessels at the skull base drain cerebrospinal fluid
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Self-citationRole of YAP/TAZ in cell-matrix adhesion-mediated signalling and mechanotransduction
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The molecular basis of endothelial cell plasticity
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Metadata
- Authors
- Sabine, A., Bovay, E., Demir, C. S., Kimura, W., Jaquet, M., Agalarov, Y., Zangger, N., Scallan, J. P., Graber, W., Gulpinar, E., Kwak, B. R., Mäkinen, T., Martinez-Corral, I., Ortega, S., Delorenzi, M., Kiefer, F., Davis, M. J., Djonov, V., Miura, N., & Petrova, T. V.
- Venue
- Journal of Clinical Investigation
- Published
- 2015-09-21
- Volume
- 125
- Issue
- 10
- Pages
- 3861-3877
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2115152359
- Cited by
- 237
- References
- 9
- FWCI
- 7.15
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Sabine, A., Bovay, E., Demir, C. S., Kimura, W., Jaquet, M., Agalarov, Y., Zangger, N., Scallan, J. P., Graber, W., Gulpinar, E., Kwak, B. R., Mäkinen, T., Martinez-Corral, I., Ortega, S., Delorenzi, M., Kiefer, F., Davis, M. J., Djonov, V., Miura, N., & Petrova, T. V. (2015). FOXC2 and fluid shear stress stabilize postnatal lymphatic vasculature. Journal of Clinical Investigation. https://doi.org/10.1172/jci80454
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