circ_2858 Helps Blood-Brain Barrier Disruption by Increasing VEGFA via Sponging miR-93-5p during Escherichia coli Meningitis

Yang, Ruicheng; Chen, Jiaqi; Xu, Bin; Yang, Bo; Fu, Jiyang; Xiao, Siyu; Tan, Chen; Chen, Huanchun; Wang, Xiangru

doi:10.1016/j.omtn.2020.09.034

Cited by 22 publications

(16 citation statements)

References 51 publications

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“…Consistently, miR-17-5p was also decreased in hBMECs in response to meningitic E. coli infection, as observed in our previous work [46]. Here, we showed that miR-17-5p was one of the competitive-sponging targets of lncRSPH9-4 and miR-17-5p could bind to 3 UTR of MMP3 to suppress the expression of MMP3.…”

Section: Discussionsupporting

confidence: 91%

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

Yang

et al. 2021

IJMS

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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, lncRSPH9-4, in meningitic E. coli infection of BMECs. LncRSPH9-4 was cytoplasm located and significantly up-regulated in meningitic E. coli-infected hBMECs. Electrical cell-substrate impedance sensing (ECIS) measurement and Western blot assay demonstrated lncRSPH9-4 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 lncRSPH9-4 regulated the permeability in hBMECs by competitively sponging miR-17-5p, thereby increasing MMP3 expression, which targeted the intercellular tight junctions. Here we reported the infection-induced lncRSPH9-4 aggravated disruption of the tight junctions in hBMECs, probably through the miR-17-5p/MMP3 axis. This finding provides new insights into the function of lncRNAs in BBB integrity during meningitic E. coli infection and provides the novel nucleic acid targets for future treatment of bacterial meningitis.

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Section: Discussionsupporting

confidence: 91%

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

Yang

et al. 2021

IJMS

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“…As accumulating evidences suggest, circRNAs can act as miRNA sponge to regulate various biological processes and gene expression [ 33 , 34 ]. In the present research, it was verified that hsa_circ_0007292 owned the stable circular structure and predominantly located in cytoplasm.…”

Section: Discussionmentioning

confidence: 99%

Hsa-circ-0007292 promotes the osteogenic differentiation of posterior longitudinal ligament cells via regulating SATB2 by sponging miR-508-3p

Jiang

Wang

Yan

et al. 2021

Aging

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Ossification of the posterior longitudinal ligament (OPLL) is a disorder with multiple pathogenic mechanisms and leads to different degrees of neurological symptoms. Recent studies have revealed that non-coding RNA (ncRNA), including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), could influence the development of OPLL. Nevertheless, the molecular mechanisms linking circular RNAs (circRNAs) and the progression of OPLL is still unknown. The current research explored the expression profiles of OPLL-related circRNAs by microarray analysis, and applied qRT-PCR to validate the results. Subsequently, we confirmed the upregulation of hsa_circ_0007292 in OPLL cells by qRT-PCR and validated the circular characteristic of hsa_circ_0007292 by Sanger sequencing. Fluorescence in situ hybridization (FISH) unveiled that hsa_circ_0007292 was predominantly located in the cytoplasm. Functionally, gain-of-function and loss-of-function experiments showed that hsa_circ_0007292 promoted the osteogenic differentiation of OPLL cells. Mechanistically, the interaction of hsa_circ_0007292 and miR-508-3p was predicted and validated by bioinformatics analysis, dual-luciferase reporter assays, and Ago2 RNA immunoprecipitation (RIP). Similarly, we validated the correlation between miR-508-3p and SATB2. Furthermore, rescue experiments were performed to prove that hsa_circ_0007292 acted as a sponge for miR-508-3p, and SATB2 was revealed to be the target gene of miR-508-3p. In conclusion, our research shows that hsa_circ_0007292 regulates OPLL progression by the miR-508-3p/SATB2 pathway. Our results indicate that hsa_circ_0007292 can be used as a promising therapeutic target for patients with OPLL.

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“…suis induction of BBB disruption is a complex process between the host and pathogen. Many studies have reported that as the most important junctional structure of BBB, the TJ proteins play important roles in maintain BBB integrity and stability of CNS microenvironment [17,54,55].…”

Section: Discussionmentioning

confidence: 99%

Two-Component Signal Transduction System VraSR Contributes to Neuroinflammation in Streptococcus Suis Meningitis

Dou

Yang

et al. 2021

Preprint

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Background: Streptococcus suis (S. suis) is an important zoonotic pathogen that can cause high morbidity and mortality in both humans and swine. As the most important life-threatening infection of the central nervous system (CNS), meningitis is an important symptom of S. suis infection. The VraSR is a critical two-component signal transduction system that affects S. suis ability to resist against host innate immune system and promotes the ability of S. suis to adhere to hBMEC. Whether and how VraSR contributes to the development of S. suis meningitis are currently unknown.Methods: The in vivo colonization, in vivo BBB permeability, histopathological examination and immunohistochemistry were applied to compare and characterize the degree of destruction of brain tissue in response to wild type SC19 and mutant ΔvraSR. Western blotting and real-time PCR were combined to identify the breakdown of tight junction proteins (TJ proteins). The secretion of proinflammatory cytokines and chemokines in the serum were detected on a BD FACSVerse flow cytometer.Results: We found an important role of VraSR regulatory system in S. suis SC19-induced meningitis. A mouse infection model demonstrated that ΔvraSR had significantly attenuated inflammatory lesions in the brain tissues compared with wild-type S. suis. In vitro, we characterized that SC19 could increase the blood-brain barrier (BBB) permeability through downregulating the TJ proteins compared with mutant ΔvraSR. Moreover, we found significant generation of proinflammatory cytokines and chemokines in the serum including IL-6, TNF-α, MCP-1, and IL-12p70 compared with ΔvraSR infected mice.Conclusions: For the first time, our work investigated the VraSR regulatory system of S. suis played an important role in streptococcal meningitis and revealed VraSR to be an important contributor to the disruption of TJ proteins. Characterization of these BBB disruption will facilitate further study of meningitis mechanisms in humans, thereby offering the development of novel preventative and therapeutic strategies against infection with S. suis.

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circ_2858 Helps Blood-Brain Barrier Disruption by Increasing VEGFA via Sponging miR-93-5p during Escherichia coli Meningitis

Cited by 22 publications

References 51 publications

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

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

Hsa-circ-0007292 promotes the osteogenic differentiation of posterior longitudinal ligament cells via regulating SATB2 by sponging miR-508-3p

Two-Component Signal Transduction System VraSR Contributes to Neuroinflammation in Streptococcus Suis Meningitis

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