In the intestinal epithelium, the aberrant regulation of cell/cell junctions leads to intestinal barrier defects, which may promote the onset and enhance the severity of inflammatory bowel disease (IBD). However, it remains unclear how the coordinated behaviour of cytoskeletal network may contribute to cell junctional dynamics. In this report, we identified ACF7, a crosslinker of microtubules and F-actin, as an essential player in this process. Loss of ACF7 leads to aberrant microtubule organization, tight junction stabilization and impaired wound closure in vitro. With the mouse genetics approach, we show that ablation of ACF7 inhibits intestinal wound healing and greatly increases susceptibility to experimental colitis in mice. ACF7 level is also correlated with development and progression of ulcerative colitis (UC) in human patients. Together, our results reveal an important molecular mechanism whereby coordinated cytoskeletal dynamics contributes to cell adhesion regulation during intestinal wound repair and the development of IBD.
[1]Tongji Univ, Shanghai Peoples Hosp 10, Dept GI Surg, 301 Yanchang Rd, Shanghai 200072, Peoples R China.
[2]Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA.
[3]Guanxi Normal Univ, State Key Lab Cultivat Base Chem & Mol Engn Med R, Minist Sci & Technol China, Guilin 541004, Peoples R China.
[4]Fudan Univ, Shanghai Canc Ctr, Dept Colorectal Surg, Shanghai, Peoples R China.
[5]Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA.
[6]Tongji Univ, Shanghai Peoples Hosp 10, Dept Pathol, 301 Yanchang Rd, Shanghai 200072, Peoples R China.
[7]Baylor Scott & White Res Inst, Ctr Epigenet Canc Prevent & Canc Genom, Ctr Gastrointestinal Res, Temple, TX USA.
[8]Charles A Sammons Canc Ctr, Dallas, TX USA.
[9]Univ Louisville, Hlth Sci Ctr, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA.
[10]Harvard Med Sch, Brigham & Womens Hosp, Dept Pathol, Boston, MA USA.
[11]Harvard Med Sch, Brigham & Womens Hosp, Dept Med GI, Boston, MA USA.
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