title: Hyaluronan 35kDa treatment protects mice from Citrobacter rodentium infection and induces epithelial tight junction protein ZO-1 in vivo.
abstract: Maintaining a healthy intestinal barrier, the primary physical barrier between intestinal microbiota and the underlying lamina propria, is critical for optimal health. Epithelial integrity is essential for the prevention of the entrance of luminal contents, such as bacteria and their products, through the large intestinal barrier. In this study, we investigated the protective functions of biosynthetic, specific sized, hyaluronan around 35kDa (HA35) on intestinal epithelium in healthy mice, as well as mice infected Citrobacter rodentium, an established model that mimics infection with a serious human pathogen, enteropathogenic E. coli (EPEC). Our results reveal that treatment with HA35 protects mice from Citrobacter infection and enhances the epithelial barrier function. In particular, we have found that HA35 induces the expression of tight junction protein zonula occludens (ZO)-1 in both healthy and Citrobacter infected mice, as demonstrated by immunoflurorescence and Western blot analyses. Furthermore, we determined that HA35 treatment enhances ZO-1 expression and reduces intestinal permeability at the early stages of dextran sulfate sodium (DSS)-induced colitis in mice. Together, our data demonstrate that the expression and functionality of tight junctions, are increased by HA35 treatment, suggesting a novel mechanism for the protection from Citrobacter infection.
authors.affiliation: Department of Pathobiology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
authors.forename: Yeojung
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Pathobiology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Kessler
authors.affiliation: Department of Pathobiology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
authors.forename: Dana R
authors.initials: DR
authors.lastname: Obery
authors.affiliation: Department of Pathobiology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
authors.forename: Craig R
authors.initials: CR
authors.lastname: Homer
authors.affiliation: Department of Pathobiology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: McDonald
authors.affiliation: Department of Pathobiology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA. Electronic address: delamoc@ccf.org.
authors.forename: Carol A
authors.initials: CA
authors.lastname: de la Motte
mesh_terms: D000284:Administration, Oral; D000818:Animals; D044082:Citrobacter rodentium / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism*; D016264:Dextran Sulfate / Q000009:adverse effects; D004195:Disease Models, Animal; D004756:Enterobacteriaceae Infections / Q000378:metabolism / Q000517:prevention & control*; D005786:Gene Expression Regulation; D006820:Hyaluronic Acid / Q000008:administration & dosage* / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D062826:Zonula Occludens-1 Protein / Q000378:metabolism*
chemical_list: C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; D006820:Hyaluronic Acid; D016264:Dextran Sulfate
keywords: Colonic epithelium; Epithelial barrier; Hyaluronan; Infection; Tight junction protein