ArticleGenome biology2023
Protocadherin 20 maintains intestinal barrier function to protect against Crohn's disease by targeting ATF6.
Article in Genome biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 18 citations in OpenAlex.
- Tripartite Interplay of Epithelial, Immune, and Microbiota Dysregulation in Crohn's Disease: Mechanisms and Translational Strategies.Immunity, inflammation and disease · 2026Review
- Macrophage SELENOP controls neutrophil homeostasis through redox stress regulation in Crohn's disease.Redox biology · 2026Article
- Downregulation of MLL1 Promotes Intestinal Epithelial Barrier Repair Through Gata4/Bmp4 Activation to Ameliorate Crohn's Disease-Like Colitis in Mice.Cell proliferation · 2026Article
- Article
- Integrative host transcriptomic and mucosal microbiome profiling reveals region-specific host-microbiome associations across the human intestine.bioRxiv : the preprint server for biology · 2026Article
- Transcriptional and ubiquitinative suppression of macrophage CST3 disrupts colonic homeostasis through defective efferocytosis.Cell death and differentiation · 2026Article
- RNF168 promotes chronic colitis through ANXA7-mediated autophagy and NLRP3-driven pyroptosis.Apoptosis : an international journal on programmed cell death · 2026Article
- Endoplasmic reticulum stress as a mechanistic link between nutrition and inflammatory bowel disease.Frontiers in nutrition · 2026Review
- [Niranthin ameliorates Crohn's disease-like enteritis in mice by inhibiting intestinal epithelial cell apoptosis and protecting intestinal barrierNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Endoplasmic reticulum stress in gut inflammation: Implications for ulcerative colitis and Crohn's disease.World journal of gastroenterology · 2025Review
- Elevated SPARC Disrupts the Intestinal Barrier Integrity in Crohn's Disease by Interacting with OTUD4 and Activating the MYD88/NF-κB Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Berberine Repairs Intestinal Mucosal Barrier by Targeting HSP90AA1 and MAPK14.Pharmacogenomics and personalized medicine · 2025Article
- Probiotics in inflammatory bowel diseases: emphasis on mechanisms and clinical application.Frontiers in medicine · 2025Review
- Research progress on the use of polyphenols in the treatment of Crohn's disease.Frontiers in pharmacology · 2025Review
- Essential roles of the unfolded protein response in intestinal physiology.eGastroenterology · 2024Review
- Identification of colon cancer subtypes based on multi-omics data-construction of methylation markers for immunotherapy.Frontiers in oncology · 2024Article
- Genomic insights into pediatric intestinal inflammatory and eosinophilic disorders using single-cell RNA-sequencing.Frontiers in immunology · 2024Article
- Protocadherin 20 maintains intestinal barrier function to protect against Crohn's disease by targeting ATF6.Genome biology · 2023Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIntestinal barrier dysfunction plays a central role in the pathological onset of Crohn's disease. We identify the cadherin superfamily member protocadherin 20 (PCDH20) as a crucial factor in Crohn's disease. Here we describe the function of PCDH20 and its mechanisms in gut homeostasis, barrier integrity, and Crohn's disease development.
resultsPCDH20 mRNA and protein expression is significantly downregulated in the colonic epithelium of Crohn's disease patients and mice with induced colitis compared with controls. In mice, intestinal-specific Pcdh20 knockout causes defects in enterocyte proliferation and differentiation, while causing morphological abnormalities. Specifically, the deletion disrupts barrier integrity by unzipping adherens junctions via β-catenin regulation and p120-catenin phosphorylation, thus aggravating colitis in DSS- and TNBS-induced colitis mouse models. Furthermore, we identify activating transcription factor 6 (ATF6), a key chaperone of endoplasmic reticulum stress, as a functional downstream effector of PCDH20. By administering a selective ATF6 activator, the impairment of intestinal barrier integrity and dysregulation of CHOP/β-catenin/p-p120-catenin pathway was reversed in Pcdh20-ablated mice with colitis and PCDH20-deficient colonic cell lines.
conclusionsPCDH20 is an essential factor in maintaining intestinal epithelial homeostasis and barrier integrity. Specifically, PCDH20 helps to protect against colitis by tightening adherens junctions through the ATF6/CHOP/β-catenin/p-p120-catenin axis.
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