Identification of urban particulate matter-induced disruption of human respiratory mucosa integrity using whole transcriptome analysis and organ-on-a chip

Junhyoung Byun, Boa Song, Kyungwoo Lee, Byoungjae Kim, Hae Won Hwang, Myung Ryul Ok, Hojeong Jeon, Kijeong Lee, Seung Kuk Baek, Sang Heon Kim, Seung Ja Oh, Tae Hoon Kim

Research output: Contribution to journalArticle

Abstract

Background: Exposure to air particulate matter (PM) is associated with various diseases in the human respiratory system. To date, most in vitro studies showing cellular responses to PM have been performed in cell culture using a single cell type. There are few studies considering how multicellular networks communicate in a tissue microenvironment when responding to the presence of PM. Here, an in vitro three-dimensional (3D) respiratory mucosa-on-a-chip, composed of human nasal epithelial cells, fibroblasts, and endothelial cells, is used to recapitulate and better understand the effects of urban particulate matter (UPM) on human respiratory mucosa. Results: We hypothesized that the first cells to contact with UPM, the nasal epithelial cells, would respond similar to the tissue microenvironment, and the 3D respiratory mucosa model would be a suitable platform to capture these events. First, whole transcriptome analysis revealed that UPM induced gene expression alterations in inflammatory and adhesion-related genes in human nasal epithelial cells. Next, we developed an in vitro 3D respiratory mucosa model composed of human nasal epithelial cells, fibroblasts, and endothelial cells and demonstrated that the model is structurally and functionally compatible with the respiratory mucosa. Finally, we used our model to expose human nasal epithelial cells to UPM, which led to a disruption in the integrity of the respiratory mucosa by decreasing the expression of zonula occludens-1 in both the epithelium and endothelium, while also reducing vascular endothelial cadherin expression in the endothelium. Conclusions: We demonstrate the potential of the 3D respiratory mucosa model as a valuable tool for the simultaneous evaluation of multicellular responses caused by external stimuli in the human respiratory mucosa. We believe that the evaluation strategy proposed in the study will move us toward a better understanding of the detailed molecular mechanisms associated with pathological changes in the human respiratory system.

Original languageEnglish
Article number88
JournalJournal of Biological Engineering
Volume13
Issue number1
DOIs
Publication statusPublished - 2019 Nov 15

Keywords

  • Cell integrity
  • Human nasal mucosa
  • Organ-on-a-chip
  • Urban particulate matter

ASJC Scopus subject areas

  • Environmental Engineering
  • Biomedical Engineering
  • Molecular Biology
  • Cell Biology

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