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Updated: Sep 8, 2025
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Measurement of Cytosolic Ca2+ in Isolated Contractile Lymphatics
Published on: December 8, 2011
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Piezo1-Regulated Mechanotransduction Controls Flow-Activated Lymphatic Expansion
Dongwon Choi1,2, Eunkyung Park1,2, Roy P Yu1
1Department of Surgery (D.C., E.P., R.P.Y., M.N.C., I.-T.C., J.C., J.Y., L.Z., J.-E.I.Y., J.S.Y., B.N., S.L., Y.J.S., W.J., Y.-K.H.), Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles' CA.
Circulation Research
|June 15, 2022
Summary
The mechanosensor Piezo1 (Piezo type mechanosensitive ion channel component 1) regulates lymphatic growth by sensing fluid flow. Piezo1 activation offers a new therapy for postsurgical lymphedema.
Area of Science:
- Cardiovascular Biology
- Cell Biology
- Physiology
Background:
- Mutations in PIEZO1 cause human lymphatic malformations.
- A previously identified ORAI1-mediated pathway regulates lymphatic sprouting via Notch signaling in response to fluid flow.
- The upstream mechanosensor for this pathway remained unidentified.
Purpose of the Study:
- To identify and characterize the molecular sensor translating external mechanical signals to ORAI1-regulated lymphatic expansion.
- To elucidate the role of Piezo1 in flow-induced lymphatic growth and regeneration.
Main Methods:
- Utilized mutant mouse models, cellular and molecular biology techniques, and a mouse tail lymphedema model.
- Investigated Piezo1 expression and function in lymphatic endothelial cells.
- Examined the effects of Piezo1 manipulation on calcium influx and downstream gene expression.
Main Results:
- Piezo1 is crucial for laminar flow-induced calcium influx and ORAI1-dependent gene regulation (KLF2, DTX1, DTX3L, NOTCH1) in lymphatic endothelial cells.
- Piezo1 activation stimulates ORAI1-regulated mechanotransduction, and Piezo1 acts upstream of ORAI1.
- Piezo1 deficiency impairs lymphatic sprouting during development and causes regression in adults; Piezo1 activation with Yoda1 ameliorates lymphedema.
Conclusions:
- Piezo1 functions as the upstream mechanosensor in the lymphatic mechanotransduction pathway, controlling lymphatic growth in response to physical stimuli.
- Piezo1 activation represents a potential therapeutic strategy for preventing postsurgical lymphedema.
- The Piezo1-lymphangiogenesis mechanism provides insight into Piezo1-associated lymphatic malformations.
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