| First Author | Ando T | Year | 2024 |
| Journal | Cells | Volume | 13 |
| Issue | 11 | PubMed ID | 38891118 |
| Mgi Jnum | J:360332 | Mgi Id | MGI:7659336 |
| Doi | 10.3390/cells13110986 | Citation | Ando T, et al. (2024) Ileal Crohn's Disease Exhibits Reduced Activity of Phospholipase C-beta3-Dependent Wnt/beta-Catenin Signaling Pathway. Cells 13(11) |
| abstractText | Crohn's disease is a chronic, debilitating, inflammatory bowel disease. Here, we report a critical role of phospholipase C-beta3 (PLC-beta3) in intestinal homeostasis. In PLC-beta3-deficient mice, exposure to oral dextran sodium sulfate induced lethality and severe inflammation in the small intestine. The lethality was due to PLC-beta3 deficiency in multiple non-hematopoietic cell types. PLC-beta3 deficiency resulted in reduced Wnt/beta-catenin signaling, which is essential for homeostasis and the regeneration of the intestinal epithelium. PLC-beta3 regulated the Wnt/beta-catenin pathway in small intestinal epithelial cells (IECs) at transcriptional, epigenetic, and, potentially, protein-protein interaction levels. PLC-beta3-deficient IECs were unable to respond to stimulation by R-spondin 1, an enhancer of Wnt/beta-catenin signaling. Reduced expression of PLC-beta3 and its signature genes was found in biopsies of patients with ileal Crohn's disease. PLC-beta regulation of Wnt signaling was evolutionally conserved in Drosophila. Our data indicate that a reduction in PLC-beta3-mediated Wnt/beta-catenin signaling contributes to the pathogenesis of ileal Crohn's disease. |
