ArticleInternational journal of molecular sciences2022
Tuning of Liver Sieve: The Interplay between Actin and Myosin Regulatory Light Chain Regulates Fenestration Size and Number in Murine Liver Sinusoidal Endothelial Cells.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Sublethal stress from polypharmacy modulates scavenging function and fenestrations in mouse liver sinusoidal endothelial cells.The Journal of pharmacology and experimental therapeutics · 2026Article
- Engineering Selenium-Chitosan Nanoparticles for Enhanced Hepatic Delivery of Sunitinib and Improved In Vitro Anticancer Activity in Hepatocellular Carcinoma Models.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Ameliorated Hepatoprotective Aptitude of Novel Lignin Nanoparticles on APAP-Induced Hepatotoxicity in a Murine Model.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Multi-cellular network model predicts alterations in glomerular endothelial structure in diabetic kidney disease.PLoS computational biology · 2025Article
- Liver Sinusoidal Endothelial Cells and Their Regulation of Immunology, Collagenization, and Bioreactivity in Fatty Liver: A Narrative Review.International journal of molecular sciences · 2025Review
- Logic-based modeling of inflammatory macrophage cross talk with glomerular endothelial cells in diabetic kidney disease.American journal of physiology. Renal physiology · 2025Article
- Article
- PACA nanoparticles target and deliver sildenafil to rejuvenate aged mouse liver sinusoidal endothelial cells.Nanotheranostics · 2025Article
- Early and late phases of liver sinusoidal endothelial cell (LSEC) defenestration in mouse model of systemic inflammation.Cellular & molecular biology letters · 2024Article
- Tubulin-Targeted Therapy in Melanoma Increases the Cell Migration Potential by Activation of the Actomyosin Cytoskeleton─An In Vitro Study.ACS biomaterials science & engineering · 2024Article
- ADAMTS18-fibronectin interaction regulates the morphology of liver sinusoidal endothelial cells.iScience · 2024Article
- Protein disulfide isomerase A1 regulates fenestration dynamics in primary mouse liver sinusoidal endothelial cells (LSECs).Redox biology · 2024Article
- Mouse liver sinusoidal endothelial cell responses to the glucocorticoid receptor agonist dexamethasone.Frontiers in pharmacology · 2024Article
- Cytochalasans and Their Impact on Actin Filament Remodeling.Biomolecules · 2023Review
- Proteomic Analysis of Dysfunctional Liver Sinusoidal Endothelial Cells Reveals Substantial Differences in Most Common Experimental Models of Chronic Liver Diseases.International journal of molecular sciences · 2023Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Liver sinusoidal endothelial cells (LSECs) facilitate the efficient transport of macromolecules and solutes between the blood and hepatocytes. The efficiency of this transport is realized via transcellular nanopores, called fenestrations. The mean fenestration size is 140 ± 20 nm, with the range from 50 nm to 350 nm being mostly below the limits of diffraction of visible light. The cellular mechanisms controlling fenestrations are still poorly understood. In this study, we tested a hypothesis that both Rho kinase (ROCK) and myosin light chain (MLC) kinase (MLCK)-dependent phosphorylation of MLC regulates fenestrations. We verified the hypothesis using a combination of several molecular inhibitors and by applying two high-resolution microscopy modalities: structured illumination microscopy (SIM) and scanning electron microscopy (SEM). We demonstrated precise, dose-dependent, and reversible regulation of the mean fenestration diameter within a wide range from 120 nm to 220 nm and the fine-tuning of the porosity in a range from ~0% up to 12% using the ROCK pathway. Moreover, our findings indicate that MLCK is involved in the formation of new fenestrations-after inhibiting MLCK, closed fenestrations cannot be reopened with other agents. We, therefore, conclude that the Rho-ROCK pathway is responsible for the control of the fenestration diameter, while the inhibition of MLCK prevents the formation of new fenestrations.
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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.