LncRSPH9-4 Facilitates Meningitic Escherichia coli-Caused Blood–Brain Barrier Disruption via miR-17-5p/MMP3 Axis

Abstract

Brain microvascular endothelial cells (BMECs) constitute the structural and functional basis for the blood-brain barrier (BBB) and play essential roles in bacterial meningitis. Although the BBB integrity regulation has been under extensive investigation, there is little knowledge regarding the roles of long non-coding RNAs (lncRNAs) in this event. The present study aimed to investigate the roles of one potential lncRNA, <i>lncRSPH9-4</i>, in meningitic <i>E. coli</i> infection of BMECs. <i>LncRSPH9-4</i> was cytoplasm located and significantly up-regulated in meningitic <i>E. coli</i>-infected hBMECs. Electrical cell-substrate impedance sensing (ECIS) measurement and Western blot assay demonstrated <i>lncRSPH9-4</i> overexpression in hBMECs mediated the BBB integrity disruption. By RNA-sequencing analysis, 639 mRNAs and 299 miRNAs were significantly differentiated in response to lncRSPH9-4 overexpression. We further found <i>lncRSPH9-4</i> regulated the permeability in hBMECs by competitively sponging <i>miR-17-5p</i>, thereby increasing MMP3 expression, which targeted the intercellular tight junctions. Here we reported the infection-induced <i>lncRSPH9-4</i> aggravated disruption of the tight junctions in hBMECs, probably through the <i>miR-17-5p</i>/MMP3 axis. This finding provides new insights into the function of lncRNAs in BBB integrity during meningitic <i>E. coli</i> infection and provides the novel nucleic acid targets for future treatment of bacterial meningitis.