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Cited by 24Lymphatic System and DiseasesLymphatic Disorders and TreatmentsHippo pathway signaling and YAP/TAZ

Mechanosensitive mTORC1 signaling maintains lymphatic valves

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Saygili Demir, Cansaran, Sabine, Amélie, Gong, Muyun, Dormond, Olivier, Petrova, Tatiana V.·2023·Journal of Cell Biology
DOI 10.1083/jcb.202207049PMC PMC10097975
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Abstract

Homeostatic maintenance and repair of lymphatic vessels are essential for health. We investigated the dynamics and the molecular mechanisms of lymphatic endothelial cell (LEC) renewal in adult mesenteric quiescent lymphatic vasculature using label-retention, lineage tracing, and cell ablation strategies. Unlike during development, adult LEC turnover and proliferation was confined to the valve regions of collecting vessels, with valve cells displaying the shortest lifespan. Proliferating valve sinus LECs were the main source for maintenance and repair of lymphatic valves. We identified mechanistic target of rapamycin complex 1 (mTORC1) as a mechanoresponsive pathway activated by fluid shear stress in LECs. Depending on the shear stress level, mTORC1 activity drives division of valve cells or dictates their mechanic resilience through increased protein synthesis. Overactivation of lymphatic mTORC1 in vivo promoted supernumerary valve formation. Our work provides insights into the molecular mechanisms of maintenance of healthy lymphatic vascular system.

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  • Once formed, valve-region LECs undergo a relatively high (10%) turnover rate compared to LECs in nonvalve regions (1%), where turnover is comparable to that of BECs.

    “Once formed, the valve-region LECs undergo a relatively high (10%) turnover rate compared to LECs in nonvalve regions (1%), where turnover is comparable to that of BECs (40).”

    From Transport and Immune Functions of the Lymphatic System. (2025) · cites this paper as [40]

    The Results section, “Lymphatic collecting vessels display higher turnover rate compared to capillaries” (Fig. 2; page not available), reports greater LEC turnover in valve areas than in lymphangions, with estimated half-lives of 9–10 versus 30–60 days. Our copy does not give the claimed 10% and 1% turnover rates or say that nonvalve LEC turnover is comparable to BEC turnover. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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Sorted by citations

Authors
Saygili Demir, C., Sabine, A., Gong, M., Dormond, O., & Petrova, T. V.
Affiliations
  • Lausanne University Hospital 1 Department of Oncology, , Lausanne, Switzerland
  • Centre Hospitalier Universitaire Vaudois (CH)
Corresponding author
Petrova, Tatiana V.
ORCID
Venue
Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2023-04-10
Volume
222
Issue
6
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
DOI
10.1083/jcb.202207049
PMC
PMC10097975
OpenAlex
W4363632303
Cited by
24
References
4
Citations by year
2026: 5 · 2025: 11 · 2024: 5 · 2023: 3
FWCI
2.93
Type
journal article
Language
en
Open access
Licence
Locations
  • The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • SERVAL (Université de Lausanne) (submittedVersion, cc-by-nc-sa)
  • IRIS (submittedVersion, cc-by-nc-sa)
Funders
  • European Union’s Horizon 2020 (847939)
  • Swiss National Science Foundation (CR32I3_166326)
  • Erna Hamburger Foundation
  • Société Académique Vaudoise
Topics
  • Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
  • Health Sciences › Medicine › Surgery › Lymphatic Disorders and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
Keywords
mTORC1 signaling, lymphatic valves, lymphatic endothelial cells, mechanotransduction, fluid shear stress, valve repair, protein synthesis, mesenteric lymphatics, valve formation
MeSH terms
Mechanistic Target of Rapamycin Complex 1, Homeostasis, Signal Transduction, Lymphangiogenesis, Lymphatic Vessels, Endothelial Cells

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Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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