Mir-203-mediated tricellulin mediates lead-induced in vitro loss of blood-cerebrospinal fluid barrier (BCB) function

Peng Su, Fang Zhao, Zipeng Cao, Jianbin Zhang, Michael Aschner, Wenjing Luo

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

The blood-cerebrospinal fluid barrier (BCB) plays a critical role in the maintenance of optimal brain function. Tricellulin (TRIC), a protein localized at the tricellular contact sites of epithelial cells is involved in the formation of tight junctions in various epithelial barriers. However, little is known about its expression in the choroidal epithelial cells. It is well established that lead (Pb) exposure increases the leakage of the BCB. The purpose of this study is to investigate the expression and localization of TRIC in choroidal epithelial cells in vitro and whether altered TRIC expression mediates Pb-induced loss of barrier function. We found that TRIC protein and mRNA were expressed in choroidal epithelial cells in vitro and TRIC was localized at the tricellular contacts, colocalizing with occludin. Downregulation of TRIC by siRNA increased the BCB permeability corroborated by altered transendothelial electrical resistance (TEER) and FITC-dextran flux. Treatment with 10. μM Pb reduced TRIC protein expression, but overexpression of TRIC alleviated the Pb-induced increase in BCB permeability. Bioinformatics analysis showed that mir-203 was a potential microRNA (miRNA) binding motif on TRIC 3. 'UTR, and that Pb exposure increased the expression of mir-203. Treatment with a mir-203 inhibitor increased TRIC protein expression and attenuated the Pb-induced BCB leakage. Our results establish that TRIC plays an important role in regulating BCB function.

Original languageEnglish (US)
Pages (from-to)1185-1194
Number of pages10
JournalToxicology in Vitro
Volume29
Issue number5
DOIs
StatePublished - Aug 1 2015

Keywords

  • Blood-cerebrospinal fluid barrier
  • Lead
  • Tricellulin

ASJC Scopus subject areas

  • Toxicology

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