ArticleCell death & disease2018
The deubiquitinating enzyme UCHL1 negatively regulates the immunosuppressive capacity and survival of multipotent mesenchymal stromal cells.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 54 citations in OpenAlex.
- METTL3-mCellular & molecular biology letters · 2026Article
- Proteomics analysis of serum extracellular vesicle identifies UCHL1 as a potential therapeutic target for high grade serous ovarian cancer.British journal of cancer · 2026Article
- Metabolic reprogramming in astrocytes prevents neuronal death through a UCHL1/PFKFB3/H4K8la positive feedback loop.Cell death and differentiation · 2025Article
- Ubiquitin C-terminal hydrolase L1 promoted pro-angiogenic capacity of periodontal ligament stem cells via HIF-1α/YAP signaling in periodontitis.Stem cell research & therapy · 2025Article
- Secretome and Proteome of Extracellular Vesicles Provide Protein Markers of Lung and Colorectal Cancer.International journal of molecular sciences · 2025Article
- Cullin 4B-RING E3 ligase negatively regulates the immunosuppressive capacity of mesenchymal stem cells by suppressing iNOS.Cell death and differentiation · 2025Article
- Exploring and analyzing two aging related genes FPR1 and UCHL1 and their potential molecular mechanisms in aggravating lumbar disc herniation.Journal of orthopaedic surgery and research · 2024Article
- Enhanced Immune Responses AgainstIndian journal of microbiology · 2024Article
- Adipose stem cell exosomes, stimulated by pro-inflammatory factors, enhance immune evasion in triple-negative breast cancer by modulating the HDAC6/STAT3/PD-L1 pathway through the transporter UCHL1.Cancer cell international · 2024Article
- Pharmacokinetic characteristics of mesenchymal stem cells in translational challenges.Signal transduction and targeted therapy · 2024Review
- Deficiency of UCHL1 results in insufficient decidualization accompanied by impaired dNK modulation and eventually miscarriage.Journal of translational medicine · 2024Article
- Identification of diagnostic markers for moyamoya disease by combining bulk RNA-sequencing analysis and machine learning.Scientific reports · 2024Article
- Mesenchymal stem cells under epigenetic control - the role of epigenetic machinery in fate decision and functional properties.Cell death & disease · 2023Review
- MSC based gene delivery methods and strategies improve the therapeutic efficacy of neurological diseases.Bioactive materials · 2023Review
- Pro-apoptotic and anti-apoptotic regulation mediated by deubiquitinating enzymes.Cellular and molecular life sciences : CMLS · 2022Review
- Single-Cell Transcriptome Analysis Reveals Mesenchymal Stem Cells in Cavernous Hemangioma.Frontiers in cell and developmental biology · 2022Article
- UCHL1 as a novel target in breast cancer: emerging insights from cell and chemical biology.British journal of cancer · 2022Review
- Investigation of HInternational journal of molecular sciences · 2021Article
- Human Wharton's jelly-derived mesenchymal stem cells alleviate concanavalin A-induced fulminant hepatitis by repressing NF-κB signaling and glycolysis.Stem cell research & therapy · 2021Article
- Growth arrest and DNA damage-inducible proteins (GADD45) in psoriasis.Scientific reports · 2021Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It is known that proinflammatory cytokines empower multipotent mesenchymal stromal cells (MSCs) the immunosuppressive capacity to treat various inflammatory diseases. Nevertheless, how the proinflammatory cytokines modulate the immunosuppressive capacity of MSCs is poorly understood. In the present study, we identified that the deubiquitinating enzyme ubiquitin C-terminal hydrolase 1 (UCHL1) was upregulated in MSCs upon stimulation of proinflammatory cytokines IFN-γ plus TNF-α. Interestingly, through intervening UCHL1 by shRNA knockdown or its inhibitor LDN57444 or overexpression, we found that UCHL1 played a critical role in suppressing cytokines-induced inducible nitric oxide synthase expression in murine MSCs and indoleamine 2,3-dioxygenase expression in human MSCs, thereby restrained their immunosuppressive capacity. This effect of UCHL1 was attributed to the negative role in regulating NF-κB and STAT1 signaling, as exhibited by promoting NF-κB and STAT1 activation upon inhibition of UCHL1. Besides, inhibition of UCHL1 suppressed cytokines-induced MSC apoptosis via upregulation of Bcl-2. As a consequence, UCHL1-inhibited MSCs effectively alleviated concanavalin A-induced inflammatory liver injury. Therefore, our study demonstrates a novel role of UCHL1 in regulating the immunosuppressive capacity and survival of MSCs, which further affects their immunotherapy for inflammatory diseases.
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