Diallyl Trisulfide, A Major Bioactive Constituent Of The Garlic, Promotes Colonic Mucosal Healing In Ulcerative Colitis Through Accelerating Focal Adhesion Assembly And Consequent Epithelial Cell Migration Via The Rab21-Integrin Β1-Fak Pathway

Scope: Colonic mucosal healing is the terminal goal for the treatment of ulcerative colitis (UC), but there is currently no specific drug available. This study investigated the beneficial effect of diallyl trisulfide (DATS) on the colonic mucosal healing.

Methods and results: Dextran sulfate sodium (DSS) was used to induce colitis in female C57BL/6 mice, and DATS was orally administered during the recovery period. DATS hardly impacted the inflammation of the colonic tissues, but significantly promoted the mucosal repair. DATS promoted the migration but not proliferation of colonic epithelial cells in the colitis mice. In addition, DATS accelerated the wound healing, cell migration, focal adhesion assembly and phosphorylation of focal adhesion kinase (FAK) of colonic epithelial cells in vitro, which were evidently reversed by combined use of FAK Inhibitor PF-573228. Similar results were shown in colitis mice. Mechanically, DATS promoted the binding of Rab21 to Integrin β1 and accelerated the endocytosis of Integrin β1, which was significantly attenuated by the knockdown of Rab21.

Conclusions: DATS promotes the binding of Rab21 to Integrin β1 and the endocytosis of Integrin β1, thereby increases FAK phosphorylation and focal adhesion assembly, finally accelerates the migration of colonic epithelial cells and mucosal healing. This article is protected by copyright. All rights reserved.

Rab21; diallyl trisulfide; focal adhesion kinase; integrin β1; mucosal healing.