Knockdown of high-mobility group nucleosome-binding protein 2 increases uropathogenic Escherichia coli invasion in human bladder epithelial cells through promoting actin cytoskeleton polymerization

High-mobility group nucleosome-binding protein 2 (HMGN2) is a non-histone nuclear protein that can bind nucleosomes and regulate chromosome architecture and gene transcription. Our previous results indicate that intranuclear HMGN2 acts as a positive modulator of NF-κB signalling to promote LPS-induced β-defensin expression. Meanwhile, HMGN2 can be released extracellularly and suppress of bacterial invasion into bladder epithelial cells (BECs). In this study, we report that intranuclear HMGN2 was also involved in the invasion of uropathogenic E. coli (UPEC) into BECs. HMGN2 knockdown resulted in elevated UPEC invasion into 5637 and T24 BECs. And HMGN2 gene silencing could induce actin polymerization, which is essential for α3/β1 integrins mediated UPEC internalization into BECs. However, the expressions of α3/β1 integrins and the phosphorylation of FAK and Src were not obviously affected by HMGN2 knockdown. Interestingly, increased expression of Rac1-GTPase was observed in HMGN2 silent BECs, which lead to actin polymerization and UPEC invasion. Furthermore, extracellular regulated protein kinases 1/2 (ERK1/2) was mostly and p38 mitogen-activated protein kinase (MAPK) was partially involved in HMGN2 silenting-mediated promotion of UPEC invasion, as confirmed with chemical inhibitors of ERK1/2 and p38 MAPK. These data suggested a potential role of HMGN2 in innate immune response during UPEC induced bladder infections.