ArticleNature communications2024
Therapeutic potential of the secreted Kazal-type serine protease inhibitor SPINK4 in colitis.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Investigating the shared genetic architecture between inflammatory bowel disease and pancreatitis: a genome-wide cross-trait analysis.Molecular genetics and genomics : MGG · 2026Pooled it
- Protease-serpin-microbiome interactions in inflammatory bowel disease: toward integrated biomarkers of gut health.Gut microbes · 2026Review
- The Serine Protease-Serine Protease Inhibitor Regulatory Network in Inflammatory Bowel Disease: From Molecular Mechanisms to Novel Therapeutic Horizons.Journal of advanced research · 2026Review
- Microbiota-derived 4-HPAA alleviates Crohn's disease by stabilizing SIRT1 and reprogramming macrophage immunometabolism.Apoptosis : an international journal on programmed cell death · 2026Article
- Single-Cell RNA Sequencing Reveals Disrupted Stromal-Epithelial Crosstalk Impairs Gut Barrier in Depression.Brain and behavior · 2026Article
- Article
- SPINK2 in hematopoiesis and cancer: Biology and clinical implications.Cell death discovery · 2026Review
- Transglutaminase 2 modulates inflammatory angiogenesis via vascular endothelial growth factor receptor 2 pathway in inflammatory bowel disease.Journal of advanced research · 2026Article
- TNF-α impairs the stria vascularis by inducing pericyte apoptosis via the NF-κB pathway in gentamicin-induced hearing loss.Journal of neuroinflammation · 2026Article
- Generative AI-augmented transcriptomic and microbiome analysis across inflammatory and fibrotic disease states in Crohn's disease.Frontiers in artificial intelligence · 2026Article
- From mucus secretion to immune surveillance: the evolving roles of goblet cells in intestinal homeostasis and inflammation.Frontiers in immunology · 2026Review
- The interaction between dendritic cells and T follicular helper cells drives inflammatory bowel disease: a review.Frontiers in immunology · 2026Review
- Epithelial cell-based multi-omics integration identifies SPINK5 and SRI as novel diagnostic biomarkers for ulcerative colitis.Frontiers in pharmacology · 2026Article
- The SPINK Protein Family in Cancer: Emerging Roles in Tumor Progression, Therapeutic Resistance, and Precision Oncology.Pharmaceuticals (Basel, Switzerland) · 2025Review
- The antiprotease Spink7 promotes inflammation resolution by modulating multiple proteases activities during wound healing.Clinical and translational medicine · 2025Article
- PTGER4 signaling regulates class IIa HDAC function and SPINK4 mRNA levels in rectal epithelial cells.Cell communication and signaling : CCS · 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
15 authors.
Funding
Abstract
Mucus injury associated with goblet cell (GC) depletion constitutes an early event in inflammatory bowel disease (IBD). Using single-cell sequencing to detect critical events in mucus dysfunction, we discover that the Kazal-type serine protease inhibitor SPINK4 is dynamically regulated in colitic intestine in parallel with disease activities. Under chemically induced colitic conditions, the grim status in Spink4-conditional knockout mice is successfully rescued by recombinant murine SPINK4. Notably, its therapeutic potential is synergistic with existing TNF-α inhibitor infliximab in colitis treatment. Mechanistically, SPINK4 promotes GC differentiation using a Kazal-like motif to modulate EGFR-Wnt/β-catenin and -Hippo pathways. Microbiota-derived diacylated lipoprotein Pam2CSK4 triggers SPINK4 production. We also show that monitoring SPINK4 in circulation is a reliable noninvasive technique to distinguish IBD patients from healthy controls and assess disease activity. Thus, SPINK4 serves as a serologic biomarker of IBD and has therapeutic potential for colitis via intrinsic EGFR activation in intestinal homeostasis.
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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.