ArticleProceedings of the National Academy of Sciences of the United States of America2024
Intracellular C3 protects β-cells from IL-1β-driven cytotoxicity via interaction with Fyn-related kinase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 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
13 citing papers in PubMed, 21 citations in OpenAlex.
- Type 2 and type 1 diabetes have opposing effects on the systemic murine complement alternative pathway.iScience · 2026Article
- Infiltrating monocytes augment alternative complement activation and exacerbate inherited retinal degeneration in a mouse model.Research square · 2026Article
- Beta-cell-specific C3 deficiency exacerbates metabolic dysregulation and insulin resistance in obesity.Molecular metabolism · 2026Article
- Intracellular C3 regulates the immune response to infection via NF-κB signaling.Cellular and molecular life sciences : CMLS · 2025Article
- Emerging roles for complement in lung transplantation.The Journal of clinical investigation · 2025Review
- Heparan sulfate fine-tuned interleukin-1 (IL-1) signaling inhibits insulin secretion of grafted pancreatic islets.Science advances · 2025Article
- The secret life of complement: challenges and opportunities in exploring functions of the complosome in disease.The Journal of clinical investigation · 2025Review
- Dual RNA-seq reveals the complement protein C3-mediated host-pathogen interaction in the brain abscess caused bymSystems · 2025Article
- The complement system in human pregnancy and preeclampsia.Frontiers in immunology · 2025Review
- Complement C3 promotes islet β-cell dedifferentiation by activating Wnt/β-catenin pathway.iScience · 2024Article
- Local complement activation and modulation in mucosal immunity.Mucosal immunology · 2024Review
- The complement system in lipid-mediated pathologies.Frontiers in immunology · 2024Review
- C3 deficiency promotes pulmonary inflammation in AT1R-induced mouse model for systemic sclerosis.Frontiers in immunology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
One of the hallmarks of type 1 but also type 2 diabetes is pancreatic islet inflammation, associated with altered pancreatic islet function and structure, if unresolved. IL-1β is a proinflammatory cytokine which detrimentally affects β-cell function. In the course of diabetes, complement components, including the central complement protein C3, are deregulated. Previously, we reported high C3 expression in human pancreatic islets, with upregulation after IL-1β treatment. In the current investigation, using primary human and rodent material and CRISPR/Cas9 gene-edited β-cells deficient in C3, or producing only cytosolic C3 from a noncanonical in-frame start codon, we report a protective effect of C3 against IL-1β-induced β-cell death, that is attributed to the cytosolic fraction of C3. Further investigation revealed that intracellular C3 alleviates IL-1β-induced β-cell death, by interaction with and inhibition of Fyn-related kinase (FRK), which is involved in the response of β-cells to cytokines. Furthermore, these data were supported by increased β-cell death in vivo in a β-cell-specific C3 knockout mouse. Our data indicate that a functional, cytoprotective association exists between FRK and cytosolic C3.
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.