ArticleCell death and differentiation2025
Cullin 4B-RING E3 ligase negatively regulates the immunosuppressive capacity of mesenchymal stem cells by suppressing iNOS.
Article in Cell death and differentiation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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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.
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Who cites it
9 citing papers in PubMed.
- METTL3-mCellular & molecular biology letters · 2026Article
- Surface marker-defined functional subpopulations of mesenchymal stromal cells: mechanisms, applications, and clinical translation.Frontiers in bioengineering and biotechnology · 2026Review
- Rearming mesenchymal stem cells with engineering strategies to combat cancer.Frontiers in immunology · 2026Review
- PARP inhibition augments immunomodulatory function of mesenchymal stem/stromal cells by promoting STAT1 phosphorylation.Stem cell research & therapy · 2025Article
- Evolution of cell therapies derived from adipose tissue: historical perspectives, current development trends and future directions.Biology direct · 2025Review
- In Vitro Analysis of PMEPA1 Upregulation in Mesenchymal Stem Cells Induced by Prostate Cancer Cells.International journal of molecular sciences · 2025Article
- Migrasomes derived from human umbilical cord mesenchymal stem cells: a new therapeutic agent for ovalbumin-induced asthma in mice.Stem cell research & therapy · 2025Article
- Enhancing Bone Repair with β-TCP-Based Composite Scaffolds: A Review of Design Strategies and Biological Mechanisms.Orthopedic research and reviews · 2025Review
- Regulation and Pharmacology of the Cyclic GMP and Nitric Oxide Pathway in Embryonic and Adult Stem Cells.Cells · 2024Review
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
Mesenchymal stem cells (MSCs) are multipotent stem cells that can exert immunomodulatory capacity upon stimulation with pro-inflammatory cytokines. Our previous work has identified Cullin 4B (CUL4B), a scaffold protein in the CUL4B-RING E3 ligase (CRL4B) complex, as a key regulator in the differentiation of MSCs. Here, we demonstrate the critical role of CUL4B in regulating the immunosuppressive function of MSCs. When stimulated with pro-inflammatory cytokines, MSCs lacking CUL4B display enhanced immunosuppressive capacity, which is mediated by the elevated inducible nitric oxide synthase (iNOS). TGF-β signaling can suppress iNOS by inhibiting its transcription as well as promoting its protein degradation. We show that the CRL4B complex cooperates with PRC2 complex and HDACs to repress transcription of Dlx1 and Pmepa1, two inhibitors of TGF-β signaling, leading to decreased expression and accelerated degradation of iNOS. Our study unveils the CRL4B complex as a potential therapeutic target in promoting the immunosuppressive capacity of MSCs.
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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.