Diallyl Trisulfide, a Major Bioactive Constituent of Garlic, Promotes Colonic Mucosal Healing in Ulcerative Colitis through Accelerating Focal Adhesion Assembly and Consequent Epithelial Cell Migration via the Rab21-Integrin beta 1-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 investigates the beneficial effect of diallyl trisulfide (DATS) on the colonic mucosal healing.Methods and results: Dextran sulfate sodium (DSS) is used to induce colitis in female C57BL/6 mice, and DATS is orally administered during the recovery period. DATS hardly impacts the inflammation of the colonic tissues, but significantly promotes the mucosal repair. DATS promotes the migration but not proliferation of colonic epithelial cells in the colitis mice. In addition, DATS accelerates the wound healing, cell migration, focal adhesion assembly, and phosphorylation of focal adhesion kinase (FAK) of colonic epithelial cells in vitro, which are evidently reversed by combined use of FAK inhibitor PF-573228. Similar results are shown in colitis mice. Mechanically, DATS promotes the binding of Rab21 to integrin beta 1 and accelerates the endocytosis of integrin beta 1, which is significantly attenuated by the knockdown of Rab21.Conclusions: DATS promotes the binding of Rab21 to integrin beta 1 and the endocytosis of integrin beta 1, thereby increases FAK phosphorylation and focal adhesion assembly, finally accelerates the migration of colonic epithelial cells and mucosal healing.