RESUMO
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.
Assuntos
Colite/etiologia , Proteínas dos Microfilamentos/fisiologia , Animais , Células CACO-2 , Adesão Celular/fisiologia , Colite/patologia , Colite/fisiopatologia , Colite Ulcerativa/etiologia , Colite Ulcerativa/patologia , Colite Ulcerativa/fisiopatologia , Cristalografia por Raios X , Modelos Animais de Doenças , Feminino , Humanos , Doenças Inflamatórias Intestinais/etiologia , Doenças Inflamatórias Intestinais/patologia , Doenças Inflamatórias Intestinais/fisiopatologia , Mucosa Intestinal/patologia , Mucosa Intestinal/fisiopatologia , Masculino , Camundongos , Camundongos Knockout , Proteínas dos Microfilamentos/química , Proteínas dos Microfilamentos/deficiência , Proteínas dos Microfilamentos/genética , Microtúbulos/fisiologia , Modelos Moleculares , Junções Íntimas/patologia , Junções Íntimas/fisiologia , Cicatrização/fisiologiaRESUMO
This corrects the article DOI: 10.1038/ncomms15375.