Piezo1 incorporates mechanical force signals into the genetic program that governs lymphatic valve development and maintenance Article Swipe
Dongwon Choi
,
Eunkyung Park
,
Eunson Jung
,
Boksik Cha
,
Somin Lee
,
James Yu
,
Paul Kim
,
Sunju Lee
,
Yeo Jin Hong
,
Chester J. Koh
,
Chang-Won Cho
,
Yifan Wu
,
Noo Li Jeon
,
Alex K. Wong
,
Laura Shin
,
S. Ram Kumar
,
Iván Bermejo-Moreno
,
R. Sathish Srinivasan
,
Il-Taeg Cho
,
Young-Kwon Hong
·
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.1172/jci.insight.125068
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.1172/jci.insight.125068
The lymphatic system plays crucial roles in tissue homeostasis, lipid absorption, and immune cell trafficking. Although lymphatic valves ensure unidirectional lymph flows, the flow itself controls lymphatic valve formation. Here, we demonstrate that a mechanically activated ion channel Piezo1 senses oscillating shear stress (OSS) and incorporates the signal into the genetic program controlling lymphatic valve development and maintenance. Time-controlled deletion of Piezo1 using a pan-endothelial Cre driver (Cdh5[PAC]-CreERT2) or lymphatic-specific Cre driver (Prox1-CreERT2) equally inhibited lymphatic valve formation in newborn mice. Furthermore, Piezo1 deletion in adult lymphatics caused substantial lymphatic valve degeneration. Piezo1 knockdown in cultured lymphatic endothelial cells (LECs) largely abrogated the OSS-induced upregulation of the lymphatic valve signature genes. Conversely, ectopic Piezo1 overexpression upregulated the lymphatic valve genes in the absence of OSS. Remarkably, activation of Piezo1 using chemical agonist Yoda1 not only accelerated lymphatic valve formation in animals, but also triggered upregulation of some lymphatic valve genes in cultured LECs without exposure to OSS. In summary, our studies together demonstrate that Piezo1 is the force sensor in the mechanotransduction pathway controlling lymphatic valve development and maintenance, and Piezo1 activation is a potentially novel therapeutic strategy for congenital and surgery-associated lymphedema.
Related Topics
Concepts
Lymphatic system
PIEZO1
Lymphatic Endothelium
Downregulation and upregulation
Lymphangiogenesis
Lymphatic vessel
Cell biology
Chemistry
Biology
Immunology
Ion channel
Gene
Genetics
Receptor
Metastasis
Cancer
Mechanosensitive channels
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1172/jci.insight.125068
- http://insight.jci.org/articles/view/125068/files/pdf
- OA Status
- gold
- Cited By
- 165
- References
- 57
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2911421449
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W2911421449Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1172/jci.insight.125068Digital Object Identifier
- Title
-
Piezo1 incorporates mechanical force signals into the genetic program that governs lymphatic valve development and maintenanceWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2019Year of publication
- Publication date
-
2019-01-24Full publication date if available
- Authors
-
Dongwon Choi, Eunkyung Park, Eunson Jung, Boksik Cha, Somin Lee, James Yu, Paul Kim, Sunju Lee, Yeo Jin Hong, Chester J. Koh, Chang-Won Cho, Yifan Wu, Noo Li Jeon, Alex K. Wong, Laura Shin, S. Ram Kumar, Iván Bermejo-Moreno, R. Sathish Srinivasan, Il-Taeg Cho, Young-Kwon HongList of authors in order
- Landing page
-
https://doi.org/10.1172/jci.insight.125068Publisher landing page
- PDF URL
-
https://insight.jci.org/articles/view/125068/files/pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://insight.jci.org/articles/view/125068/files/pdfDirect OA link when available
- Concepts
-
Lymphatic system, PIEZO1, Lymphatic Endothelium, Downregulation and upregulation, Lymphangiogenesis, Lymphatic vessel, Cell biology, Chemistry, Biology, Immunology, Ion channel, Gene, Genetics, Receptor, Metastasis, Cancer, Mechanosensitive channelsTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
165Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 19, 2024: 26, 2023: 27, 2022: 33, 2021: 33Per-year citation counts (last 5 years)
- References (count)
-
57Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.OSS. | 124, 156 |
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| abstract_inverted_index.Yoda1 | 132 |
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| abstract_inverted_index.mice. | 80 |
| abstract_inverted_index.novel | 185 |
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