S100A4 Contributes To Colitis Development By Increasing The Adherence Of Citrobacter Rodentium To Intestinal Epithelial Cells

Inflammatory bowel disease(IBD)is a chronic inflammatory disorder.Amounts of factors can promote IBD development and the effective mechanisms of host defense are crucial.S100A4 is a member of S100 protein family and its role in inflammation is not clear.Therefore,we orally inoculated S100A4 knockout(S100A4-/-)mice and wild type(WT)mice with 2 × 109 CFU(Colony-forming unit)Citrobacter rodentium(C.rodentium)to investigate the role of S100A4 in colitis and the underlying mechanism through histology,cytology and molecular biology techniques.Resuls reveal that the mRNA expression of S100A4 is up-regulated in the colon of C.rodentium-infected mice.The C.rodentium infection-induced weight loss and colonic pathology was attenuated in S100A4-/-mice(P < 0.05).Moreover,the expression of chemokines,inflammatory cytokines and phosphorylation of p65(p-p65)declined in S100A4-/-mice compared with WT mice(P < 0.05)as well as the infiltration of macrophages and neutrophils decreased significantly in S100A4-/-mice colon(P < 0.01).Our results showed that S100A4 could promote the development of colitis.The percentage of Ki-67+ cells decreased significantly in S100A4-/-mice colon compared with WT mice(P < 0.05)and phosphorylation of Stat3,Erk in S100A4-/-mice down-regulated significantly.Results revealed that S100A4 promoted cell proliferation induced by C.rodentium.Further study indicated that S100A4 could increase the adherence of C.rodentium to intestinal epithelial cells and CT26 cells(P < 0.05)and the mRNA expression of Integrin ?1 is up-regulated in WT mice colon as well as in CT26 cells administrated with S100A4(P < 0.05).Our results showed that S100A4 could promote the development of colitis by increasing the adherence of C.rodentium to intestinal epithelial cells with the up-regulating expression of Integrin ?1 and promoted cell proliferation induced by C.rodentium.This study provides theoretical basis for revealing the molecular mechanism of colitis and a reference for clinical treatment.