ArticleCurrent biology : CB2016
Cyclic Mechanical Loading Is Essential for Rac1-Mediated Elongation and Remodeling of the Embryonic Mitral Valve.
Article in Current biology : CB, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 46 citations in OpenAlex.
- Influence of atrial septal defect on mitral valve growth after repair of coarctation of the aorta or an interrupted aortic arch in infants.Clinical and experimental pediatrics · 2026Article
- Spatiotemporal Atlas of Heart Development Reveals Blood-Flow-Dependent Cellular, Structural, Metabolic, and Spatial Remodeling.bioRxiv : the preprint server for biology · 2025Article
- Differential Development of the Chordae Tendineae and Anterior Leaflet of the Bovine Mitral Valve.Journal of cardiovascular development and disease · 2024Article
- IOP and glaucoma damage: The essential role of optic nerve head and retinal mechanosensors.Progress in retinal and eye research · 2024Review
- Topographical cues of biomaterials and fibroblast activation: Are they related?Mechanobiology in medicine · 2024Review
- FilGAP regulates tumor growth in Glioma through the regulation of mTORC1 and mTORC2.Scientific reports · 2023Article
- Quantitative 4D imaging of biomechanical regulation of ventricular growth and maturation.Current opinion in biomedical engineering · 2023Article
- Shear and hydrostatic stress regulate fetal heart valve remodeling through YAP-mediated mechanotransduction.eLife · 2023Article
- Soft, strong, tough, and durable protein-based fiber hydrogels.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Optineurin links Hace1-dependent Rac ubiquitylation to integrin-mediated mechanotransduction to control bacterial invasion and cell division.Nature communications · 2022Article
- Mechanical strain stimulates COPII-dependent secretory trafficking via Rac1.The EMBO journal · 2022Article
- An injury-responsive Rac-to-Rho GTPase switch drives activation of muscle stem cells through rapid cytoskeletal remodeling.Cell stem cell · 2022Article
- Flow-Mediated Factors in the Pathogenesis of Hypoplastic Left Heart Syndrome.Journal of cardiovascular development and disease · 2022Review
- DCHS1, Lix1L, and the Septin Cytoskeleton: Molecular and Developmental Etiology of Mitral Valve Prolapse.Journal of cardiovascular development and disease · 2022Article
- Hydrostatic mechanical stress regulates growth and maturation of the atrioventricular valve.Development (Cambridge, England) · 2021Article
- Mechanosensitive Pathways in Heart Development: Findings from Chick Embryo Studies.Journal of cardiovascular development and disease · 2021Review
- On Valve Interstitial Cell Signaling: The Link Between Multiscale Mechanics and Mechanobiology.Cardiovascular engineering and technology · 2021Review
- On the role of predicted in vivo mitral valve interstitial cell deformation on its biosynthetic behavior.Biomechanics and modeling in mechanobiology · 2021Article
- Computational Modeling of Blood Flow Hemodynamics for Biomechanical Investigation of Cardiac Development and Disease.Journal of cardiovascular development and disease · 2021Review
- Evaluation of active Rac1 levels in cancer cells: A case of misleading conclusions from immunofluorescence analysis.The Journal of biological chemistry · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
During valvulogenesis, globular endocardial cushions elongate and remodel into highly organized thin fibrous leaflets. Proper regulation of this dynamic process is essential to maintain unidirectional blood flow as the embryonic heart matures. In this study, we tested how mechanosensitive small GTPases, RhoA and Rac1, coordinate atrioventricular valve (AV) differentiation and morphogenesis. RhoA activity and its regulated GTPase-activating protein FilGAP are elevated during early cushion formation but decreased considerably during valve remodeling. In contrast, Rac1 activity was nearly absent in the early cushions but increased substantially as the valve matured. Using gain- and loss-of-function assays, we determined that the RhoA pathway was essential for the contractile myofibroblastic phenotype present in early cushion formation but was surprisingly insufficient to drive matrix compaction during valve maturation. The Rac1 pathway was necessary to induce matrix compaction in vitro through increased cell adhesion, elongation, and stress fiber alignment. Facilitating this process, we found that acute cyclic stretch was a potent activator of RhoA and subsequently downregulated Rac1 activity via FilGAP. On the other hand, chronic cyclic stretch reduced active RhoA and downstream FilGAP, which enabled Rac1 activation. Finally, we used partial atrial ligation experiments to confirm in vivo that altered cyclic mechanical loading augmented or restricted cushion elongation and thinning, directly through potentiation of active Rac1 and active RhoA, respectively. Together, these results demonstrate that cyclic mechanical signaling coordinates the RhoA to Rac1 signaling transition essential for proper embryonic mitral valve remodeling.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.