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MicroRNA regulatory networks reflective of polyhexamethylene guanidine phosphate-induced fibrosis in A549 human alveolar adenocarcinoma cells.

Authors
  • Shin, Da Young1
  • Jeong, Mi Ho1
  • Bang, In Jae1
  • Kim, Ha Ryong2
  • Chung, Kyu Hyuck3
  • 1 School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, 16419, Republic of Korea. , (North Korea)
  • 2 College of Pharmacy, Catholic University of Daegu, Gyeongsan, Gyeongsangbuk-do, 38430, Republic of Korea. Electronic address: [email protected] , (North Korea)
  • 3 School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, 16419, Republic of Korea. Electronic address: [email protected] , (North Korea)
Type
Published Article
Journal
Toxicology letters
Publication Date
May 01, 2018
Volume
287
Pages
49–58
Identifiers
DOI: 10.1016/j.toxlet.2018.01.010
PMID: 29337256
Source
Medline
Keywords
License
Unknown

Abstract

Polyhexamethylene guanidine phosphate (PHMG-phosphate), an active component of humidifier disinfectant, is suspected to be a major cause of pulmonary fibrosis. Fibrosis, induced by recurrent epithelial damage, is significantly affected by epigenetic regulation, including microRNAs (miRNAs). The aim of this study was to investigate the fibrogenic mechanisms of PHMG-phosphate through the profiling of miRNAs and their target genes. A549 cells were treated with 0.75 μg/mL PHMG-phosphate for 24 and 48 h and miRNA microarray expression analysis was conducted. The putative mRNA targets of the miRNAs were identified and subjected to Gene Ontology analysis. After exposure to PHMG-phosphate for 24 and 48 h, 46 and 33 miRNAs, respectively, showed a significant change in expression over 1.5-fold compared with the control. The integrated analysis of miRNA and mRNA microarray results revealed the putative targets that were prominently enriched were associated with the epithelial-mesenchymal transition (EMT), cell cycle changes, and apoptosis. The dose-dependent induction of EMT by PHMG-phosphate exposure was confirmed by western blot. We identified 13 putative EMT-related targets that may play a role in PHMG-phosphate-induced fibrosis according to the Comparative Toxicogenomic Database. Our findings contribute to the comprehension of the fibrogenic mechanism of PHMG-phosphate and will aid further study on PHMG-phosphate-induced toxicity.

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