期刊
FASEB JOURNAL
卷 31, 期 9, 页码 3922-3933出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.201700180R
关键词
adherens junctions; tight junctions; oral cavity
资金
- Dutch Organization for Scientific Research (NWO) [ALW2PJ/09070]
- International Team for Implantology (Basel, Switzerland) (ITI) [1091_2015]
- Academic Proof-of-Concept fund of the municipality of Amsterdam
- University of Amsterdam
Histatins are multifunctional histidine-rich peptides secreted by the salivary glands and exclusively present in the saliva of higher primates, where they play a fundamental role in the protection of the oral cavity. Our previously published results demonstrated that histatin-1 (Hst1) promotes cell-substrate adhesion in various cell types and hinted that it could also be involved in cell-cell adhesion, a process of fundamental importance to epithelial and endothelial barriers. Here we explore the effects of Hst1 on cellular barrier function. We show that Hst1 improved endothelial barrier integrity, decreased its permeability for large molecules, and prevented translocation of bacteria across epithelial cell layers. These effects are mediated by the adherens junction protein E-cadherin (E-cad) and by the tight junction protein zonula occludens 1, as Hst1 increases the levels of zonula occludens 1 and of active E-cad. Hst1 may also promote epithelial differentiation as Hst1 induced transcription of the epithelial cell differentiation marker apolipoprotein A-IV (a downstream E-cad target). In addition, Hst1 counteracted the effects of epithelial-mesenchymal transition inducers on the outgrowth of oral cancer cell spheroids, suggesting that Hst1 affects processes that are implicated in cancer progression.
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