Hepatocyte Growth Factor Alters Renal Epithelial Cell Susceptibility to Uropathogenic Escherichia coli

Abstract

ABSTRACT. The urinary tract is frequently the source of Escherichia coli bacteremia. Bacteria from the urinary tract must cross an epithelial layer to enter the bloodstream. Hepatocyte growth factor (HGF) alters the polarity of Madin-Darby canine kidney (MDCK) epithelial cells. The role of cell polarity in determining renal epithelial resistance to Escherichia coli invasion is not well known. A model of polarized and HGF-treated MDCK epithelial cells grown on filters was used to study the role of epithelial cell polarity during the interaction of nonvirulent (XL1-Blue) and uropathogenic (J96) strains of Escherichia coli with renal epithelium. Basolateral exposure of MDCK cells to J96, but not XL1-Blue, resulted in loss of transepithelial resistance (TER), which was due to epithelial cytotoxicity and not degradation of epithelial junctional proteins by bacterial proteases. Apical exposure to both J96 and XL1-Blue did not alter TER. Pretreatment of polarized MDCK cell monolayers with HGF renders the cells sensitive to loss of TER and cytotoxicity by apical exposure to J96. Analysis by confocal microscopy demonstrated that HGF treatment of MDCK cell monolayers also greatly enhances adherence of J96 to the apical surface of the cell monolayer. These data demonstrate that the basolateral surface of polarized epithelia is more susceptible to J96 cytotoxicity. The data also support the hypothesis that processes that alter epithelial cell polarity increase sensitivity of epithelia to bacterial injury and adherence from the apical compartment.

Identification of Interaction Partners of Outer Inflammatory Protein A: Computational and Experimental Insights into How Helicobacter pylori Infects Host Cells

“…Preclinical research on injury/disease models, such as acute tissue injury, chronic fibrosis, cardiovascular illness, and neurodegenerative disorders, have been carried out to address the therapeutic importance of HGF. HGF/c-Met signaling pathway was also associated with the polarity of the epithelial cell that affects the cell susceptibility to pathogenic microorganism (Wu, Billings et al 2001). Importantly, HGF/c-Met signaling pathway is targeted by one of the important virulence factors, CagA resulting in enhancement of cell scattering which is an indicator of the motogenic response of H. pylori -infected gastric epithelial cells (Furge, Zhang et al 2000, Churin, Al-Ghoul et al 2003, Franke, Müller et al 2008).…”

“…Preclinical research on injury/disease models, such as acute tissue injury, chronic fibrosis, cardiovascular illness, and neurodegenerative disorders, have been carried out to address the therapeutic importance of HGF. HGF/c-Met signaling pathway was also associated with the polarity of the epithelial cell that affects the cell susceptibility to pathogenic microorganism (Wu, Billings et al 2001).…”