Non-histone nuclear protein HMGN2 differently regulates the urothelium barrier function by altering expression of antimicrobial peptides and tight junction protein genes in UPEC J96-infected bladder epithelial cell monolayer

Hanwen Tian; Junming Miao; Fumei Zhang; Feng Xiong; Feimei Zhu; Jinyu Li; Xiaoying Wang; Shanzhe Chen; Junli Chen; Ning Huang; Yi Wang

doi:10.18388/abp.2017_1622

Hanwen Tian Research Unit of Infection and Immunity, Department of Pathophysiology, West China College of Basic and Forensic Medicine, Sichuan University, Chengdu 610041, China, Department of Pharmacology, West China College of Basic and Forensic Medicine, Sichuan University, Chengdu 610041, China
Junming Miao Research Unit of Infection and Immunity, Department of Pathophysiology, West China College of Basic and Forensic Medicine, Sichuan University, Chengdu 610041, China
Fumei Zhang Experimental Center, Northwest University for Nationalities, Lanzhou 730030, China
Feng Xiong Department of Cardiology, The Third People’s Hospital of Chengdu, Chengdu, China
Feimei Zhu Research Unit of Infection and Immunity, Department of Pathophysiology, West China College of Basic and Forensic Medicine, Sichuan University, Chengdu 610041, China
Jinyu Li Research Unit of Infection and Immunity, Department of Pathophysiology, West China College of Basic and Forensic Medicine, Sichuan University, Chengdu 610041, China
Xiaoying Wang Research Unit of Infection and Immunity, Department of Pathophysiology, West China College of Basic and Forensic Medicine, Sichuan University, Chengdu 610041, China
Shanzhe Chen Research Unit of Infection and Immunity, Department of Pathophysiology, West China College of Basic and Forensic Medicine, Sichuan University, Chengdu 610041, China
Junli Chen Research Unit of Infection and Immunity, Department of Pathophysiology, West China College of Basic and Forensic Medicine, Sichuan University, Chengdu 610041, China
Ning Huang Research Unit of Infection and Immunity, Department of Pathophysiology, West China College of Basic and Forensic Medicine, Sichuan University, Chengdu 610041, China
Yi Wang Research Unit of Infection and Immunity, Department of Pathophysiology, West China College of Basic and Forensic Medicine, Sichuan University, Chengdu 610041, China

DOI: https://doi.org/10.18388/abp.2017_1622

Abstract

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 non-histone nuclear protein HMGN2 in lung epithelial innate immune response. In the study presented here, 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 junction (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 different modulations of intracellular and paracellular routes through which UPEC invades the bladder epithelium.