High mobility group nucleosomal binding 2 reduces integrin α5/β1-mediated adhesion of Klebsiella pneumoniae on Human pulmonary Epithelial cells via Nuclear factor I.

It has been reported that High mobility group nucleosomal binding domain 2 (HMGN2) is a nucleus-related protein to regulate gene transcription and plays a critical role in bacterial clearance. We have demonstrated that an elevated level of HMGN2 reduced integrin α5/β1 expression of human pulmonary epithelial A549 cells during Klebsiella pneumoniae infection, thus weakening bacteric adhesion and invasion. However, the mechanism of how HMGN2 regulates integrin expression remains unclear. In this study, we found that a transcription factor-Nuclear factor I (NFI), which served as the potential target of HMGN2 to regulate integrin expression. Our results showed that HMGN2 was able to promote NFIA and NFIB expression by increasing H3K27 acetylation of NFIA/B promoter regions. The integrin α5/β1 expression was significantly enhanced by knockdown of NFIA/B via siRNA approach. Meanwhile, NFIA/B silence could also compromise the inhibition effect of HMGN2 on the integrin α5/β1 expression. Mechanistically, we demonstrated that HMGN2 facilitated the recruitment of NFI on the promoter regions of integrin α5/β1 according to the Chromatin immunoprecipitation assay. In addition, we further demonstrated that the knockdown of NFIA/B induced more adhesion of Klebsiella pneumoniae on pulmonary epithelial A549 cells, which could be reversed by the application of an integrin inhibitor RGD. Our results revealed a regulatory role of HMGN2 on the transcription level of integrin α5/β1, indicating a potential treatment strategy against Klebsiella pneumoniae-induced lung infectious diseases. This article is protected by copyright. All rights reserved.