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Mechanosensitive mTORC1 signaling maintains lymphatic valves
Cansaran Saygili Demir1,2, Amélie Sabine1,2, Muyun Gong1,2
1Department of Oncology, Lausanne University Hospital-University of Lausanne, Lausanne, Switzerland.
The Journal of Cell Biology
|April 10, 2023
Summary
Adult lymphatic endothelial cell (LEC) renewal occurs mainly at valve regions. The mechanistic target of rapamycin complex 1 (mTORC1) pathway, activated by shear stress, regulates LEC division and protein synthesis for lymphatic valve maintenance and repair.
Area of Science:
- Vascular Biology
- Cellular Dynamics
- Molecular Mechanisms
Background:
- Homeostatic maintenance and repair of lymphatic vessels are crucial for overall health.
- Understanding lymphatic endothelial cell (LEC) renewal in adult quiescent vasculature is essential.
Purpose of the Study:
- To investigate the dynamics and molecular mechanisms of LEC renewal in adult mesenteric lymphatic vasculature.
- To identify key pathways regulating LEC turnover and lymphatic valve maintenance.
Main Methods:
- Employed label-retention, lineage tracing, and cell ablation strategies.
- Focused on adult mesenteric quiescent lymphatic vasculature.
Main Results:
- Adult LEC turnover and proliferation were localized to collecting vessel valve regions.
- Valve LECs exhibited the shortest lifespan and were the primary source for valve maintenance and repair.
- Mechanistic target of rapamycin complex 1 (mTORC1) was identified as a mechanoresponsive pathway activated by fluid shear stress.
Conclusions:
- mTORC1 activity, dependent on shear stress levels, drives valve cell division or enhances mechanic resilience via protein synthesis.
- In vivo overactivation of lymphatic mTORC1 led to supernumerary valve formation.
- This study provides critical insights into the molecular mechanisms governing the maintenance of a healthy lymphatic vascular system.
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