High mobility group box 1-induced epithelial mesenchymal transition in human airway epithelial cells

Yu Ching Chen, Sarah Statt, Reen Wu, Hao Teng Chang, Jiunn Wang Liao, Chien Neng Wang, Woei Cherng Shyu, Chen Chen Lee

Research output: Contribution to journalArticle

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Abstract

Epithelial-mesenchymal transition (EMT) is implicated in bronchial remodeling and loss of lung function in chronic inflammatory airway diseases. Previous studies showed the involvement of the high mobility group box 1 (HMGB1) protein in the pathology of chronic pulmonary inflammatory diseases. However, the role of HMGB1 in EMT of human airway epithelial cells is still unclear. In this study, we used RNA sequencing to show that HMGB1 treatment regulated EMT-related gene expression in human primary-airway epithelial cells. The top five upregulated genes were SNAI2, FGFBP1, VIM, SPARC (osteonectin), and SERPINE1, while the downregulated genes included OCLN, TJP1 (ZO-1), FZD7, CDH1 (E-cadherin), and LAMA5. We found that HMGB1 induced downregulation of E-cadherin and ZO-1, and upregulation of vimentin mRNA transcription and protein translation in a dose-dependent manner. Additionally, we observed that HMGB1 induced AKT phosphorylation, resulting in GSK3β inactivation, cytoplasmic accumulation, and nuclear translocation of β-catenin to induce EMT in human airway epithelial cells. Treatment with PI3K inhibitor (LY294006) and β-catenin shRNA reversed HMGB1-induced EMT. Moreover, HMGB1 induced expression of receptor for advanced glycation products (RAGE), but not that of Toll-like receptor (TLR) 2 or TLR4, and RAGE shRNA inhibited HMGB1-induced EMT in human airway epithelial cells. In conclusion, we found that HMGB1 induced EMT through RAGE and the PI3K/AKT/GSK3β/β-catenin signaling pathway.

Original languageEnglish (US)
Article number18815
JournalScientific Reports
Volume6
DOIs
StatePublished - Jan 7 2016

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Epithelial-Mesenchymal Transition
Epithelial Cells
Catenins
Cadherins
Protein Biosynthesis
Phosphatidylinositol 3-Kinases
Small Interfering RNA
Down-Regulation
Osteonectin
HMGB1 Protein
RNA Sequence Analysis
Toll-Like Receptor 2
Vimentin
Lung Diseases
Genes
Up-Regulation
Phosphorylation
Pathology
Gene Expression
Lung

ASJC Scopus subject areas

  • General

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High mobility group box 1-induced epithelial mesenchymal transition in human airway epithelial cells. / Chen, Yu Ching; Statt, Sarah; Wu, Reen; Chang, Hao Teng; Liao, Jiunn Wang; Wang, Chien Neng; Shyu, Woei Cherng; Lee, Chen Chen.

In: Scientific Reports, Vol. 6, 18815, 07.01.2016.

Research output: Contribution to journalArticle

Chen, Yu Ching ; Statt, Sarah ; Wu, Reen ; Chang, Hao Teng ; Liao, Jiunn Wang ; Wang, Chien Neng ; Shyu, Woei Cherng ; Lee, Chen Chen. / High mobility group box 1-induced epithelial mesenchymal transition in human airway epithelial cells. In: Scientific Reports. 2016 ; Vol. 6.
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