ArticleCell death & disease2026
Tryptophan metabolic gatekeeping in epithelial repair: GPR35-KLF5 circuitry decodes mucosal damage signals for repair programming.
Article in Cell death & disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 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
3 citing papers in PubMed.
- GPR35 Mediates the Proliferation and Adipogenesis of Goat Intramuscular Preadipocytes Through the cAMP/PKA Signaling Pathway.Animals : an open access journal from MDPI · 2026Article
- Identification of Ellagic Acid as a Natural GPR35 Agonist for Ulcerative Colitis Therapy.Biomolecules · 2026Article
- Unraveling the pleiotropic roles of the mTOR-glycolytic axis in ulcerative colitis: from immunometabolic dysregulation to mucosal barrier remodeling.Frontiers in immunology · 2026Review
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
The impaired repair of intestinal mucosal damage is an important pathological feature of ulcerative colitis (UC). The critical role of intestinal epithelial cells (IECs) proliferation and migration in the repair of damaged mucosal epithelium has been well established. However, the molecular circuitry that decodes IECs sense intestinal mucosal damage signals to initiate and drive repair program remains elusive. Here, we identify a tryptophan (Trp) metabolic gatekeeping mechanism wherein G protein-coupled receptor 35 (GPR35) senses intestinal mucosal damage through monitoring Trp-kynurenine (KYN)-kynurenic acid (KA) axis metabolism with a unique "sandwich" structural binding mode. We delineate a GPR35-Kruppel-like factor 5 (KLF5) regulatory circuit in which KLF5 serves as the central effector, translating GPR35-mediated KA sensing into repair programming through PI3K-AKT-mTOR signaling cascade. This circuitry precisely orchestrates IECs proliferation and migration by regulating KLF5-dependent gene expression networks that essential for restoring damaged mucosa. Once this metabolic gatekeeping system is disrupted, either through impaired GPR35-mediated KA sensing or defective signal transduction, compromises damage signal decoding, leading to inadequate repair responses. Such dysregulation results in delayed intestinal mucosal repair and exacerbation of tissue damage. Our findings highlight GPR35 as a surveillant of abnormal Trp-KYN-KA axis metabolism, enabling IECs to detect intestinal mucosal damage and orchestrate repair through KLF5 response. This provides important implications for UC prevention and treatment by targeting GPR35-KLF5 circuit.
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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 Socratic graph.