Arctigenin promotes mucosal healing in ulcerative colitis through facilitating focal adhesion assembly and colonic epithelial cell migration via targeting focal adhesion kinase.

Colonic mucosal defect constitutes the major reason of recurrence and deterioration of ulcerative colitis (UC), and mucosal healing has become the therapeutic endpoint of UC. Unfortunately, specific promoter of mucosal healing is still absent. Our previous researches demonstrated that arctigenin could alleviate colitis symptoms in mice, but whether it has a positive impact on colonic mucosal healing remains unclear. This study explores whether and how arctigenin promotes mucosal healing. Orally administered arctigenin was shown to alleviate colitis in mice primarily by enhancing mucosal healing. In vitro, arctigenin was shown to promote the wound healing by accelerating colonic epithelial cell migration but not proliferation. Acceleration of the focal adhesion turnover, especially assembly, is crucial for arctigenin promoting the cell migration. Arctigenin was able to activate focal adhesion kinase (FAK) in colonic epithelial cells through directly binding with Tyr251 site of FAK, as evidenced by surface plasmon resonance assay and site-directed mutagenesis experiment. In the colonic epithelial cells of UC patients and colitis mice, FAK activation was significantly down-regulated compared with the controls. Arctigenin promoted colonic epithelial cell migration and mucosal healing in dextran sulphate sodium (DSS)-induced colitis mice dependent on activating FAK, as confirmed by combined use with FAK inhibitor. In summary, arctigenin can directly promote mucosal healing in colitis mice through facilitating focal adhesion turnover, especially assembly, and consequent migration of epithelial cells via targeting FAK. Arctigenin may be developed as a mucosal healing promoter, and FAK is a potential therapeutic target for UC and other mucosal defect-related diseases.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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