Myofibroblast Derived Transglutaminase 2 Activity is Upregulated in Stricturing Crohn's Disease and its Inhibition Exerts Anti-Fibrotic Properties.

Transglutaminase 2 activity is up to 100% attributable to myofibroblasts in strictured Crohn's disease and correlates with tissue fibrosis severity.

• Why it matters: Understanding the mechanisms behind intestinal fibrosis is crucial because it progresses independently of inflammation, complicating treatment strategies for Crohn's disease.
• What they did: Researchers measured TG2 expression and activity in human tissues and HIMF, used inhibitors and genetic knockout models, and validated signaling pathways through RNA sequencing techniques.
• The result: Inhibition of TG2 activity reduced ECM component accumulation and prevented experimental fibrosis, suggesting TG2's role in inflammation-independent fibrosis progression.