Inflammatory fibroblasts and epithelial-mesenchymal plasticity in inflammatory bowel disease
Inflammatory fibroblasts and epithelial-mesenchymal plasticity in inflammatory bowel disease
Intestinal fibrosis is a serious complication of inflammatory bowel disease (IBD). It develops when long-lasting inflammation triggers excessive scar tissue formation in the intestinal wall. Over time, this can narrow the intestine, cause obstruction, and eventually make surgery necessary.
This thesis of Li Wang investigated how intestinal fibrosis develops and whether existing or potential treatments can interfere with this process. The studies show that not every inflammatory signal that activates intestinal fibroblasts is sufficient to trigger fibrosis. TGF-β signaling remains a central driver of fibroblast activation and fibrotic changes.
This thesis also explored how different drugs influence fibroblast behavior. Upadacitinib and pirfenidone were found to reduce the expression of IL13RA2, a receptor associated with inflamed intestinal tissue and activated fibroblast states. In addition, inflammatory and fibrotic signals were shown to induce reversible epithelial changes in human intestinal organoids. These changes could be prevented by blocking TGF-β-related signaling.
Together, these thesis shows that intestinal fibrosis is driven by several interacting cellular processes rather than by a single pathway. They also suggest that successful anti-fibrotic treatment may require targeting both fibroblast activation and changes in the intestinal epithelium. There are existing drugs that can be useful for developing new anti-inflammatory and anti-fibrotic strategies for patients with IBD.