High-mobility group nucleosomal binding domain 2 differently regulates urothelium barrier function by altering expression of antimicrobial peptides and tight junction proteins gene in UPEC J96-infected bladder epithelial cell monolayer

The urinary tract is vulnerable to frequent challenges from environmental microflora. Uropathogenic Escherichia coli (UPEC) makes a major contribution to urinary tract infection (UTI). Previous studies have characterized positive roles of high-mobility group nucleosomal binding domain 2 (HMGN2), a non-histone nuclear protein, in lung epithelial innate immune response. In the present study, we found HMGN2 expression was up-regulated in UPEC J96-infected urothelium. Surprisingly, over-expression of HMGN2 promoted disruption of BECs 5637 cells intercellular junctions by down-regulating tight junctions (TJs) components expression and physical structure under J96 infection. Further investigation showed that BECs 5637 monolayer, in which HMGN2 was over-expressed, had significantly increased permeability to J96. Our study systemically explored the regulatory roles of HMGN2 in BECs barrier function during UPEC infection and suggested difference modulations on intracellular and paracellular routes through which UPEC invasion in bladder epithelium.