Tryptophan metabolic gatekeeping in epithelial repair: GPR35-KLF5 circuitry decodes mucosal damage signals for repair programming.

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 effecto

SUBMITTER: Xie B 

PROVIDER: S-EPMC12789062 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature