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Time-course transcriptomic alterations reflect the pathophysiology of polyhexamethylene guanidine phosphate-induced lung injury in rats.
Inhal Toxicol. 2019 Nov - Dec; 31(13-14):457-467.IT

Abstract

Objective:

Humidifier-disinfectant-induced lung injury is a new syndrome associated with a high mortality rate and characterized by severe hypersensitivity pneumonitis, acute interstitial pneumonia, or acute respiratory distress syndrome. Polyhexamethylene guanidine phosphate (PHMG-P), a guanidine-based antimicrobial agent, is a major component associated with severe lung injury. In-depth studies are needed to determine how PHMG-P affects pathogenesis at the molecular level. Therefore, in this study, we analyzed short-term (4 weeks) and long-term (10 weeks) PHMG-P-exposure-specific gene-expression patterns in rats to improve our understanding of time-dependent changes in fibrosis.Materials and methods: Gene-expression profiles were analyzed in rat lung tissues using DNA microarrays and bioinformatics tools.

Results:

Clustering analysis of gene-expression data showed different gene-alteration patterns in the short- and long-term exposure groups and higher sensitivity to gene-expression changes in the long-term exposure group than in the short-term exposure group. Supervised analysis revealed 34 short-term and 335 long-term exposure-specific genes, and functional analysis revealed that short-term exposure-specific genes were involved in PHMG-P-induced initial inflammatory responses, whereas long-term exposure-specific genes were involved in PHMG-P-related induction of chronic lung fibrosis.

Conclusion:

The results of transcriptomic analysis were consistent with lung histopathology results. These findings indicated that exposure-time-specific changes in gene expression closely reflected time-dependent pathological changes in PHMG-P-induced lung injury.

Authors+Show Affiliations

National Center for Efficacy Evaluation for Respiratory Disease Product, Korea Institute of Toxicology, Jeongeup, Republic of Korea. Department of Human and Environmental Toxicology, University of Science and Technology, Daejeon, Republic of Korea.National Center for Efficacy Evaluation for Respiratory Disease Product, Korea Institute of Toxicology, Jeongeup, Republic of Korea.National Center for Efficacy Evaluation for Respiratory Disease Product, Korea Institute of Toxicology, Jeongeup, Republic of Korea. Department of Human and Environmental Toxicology, University of Science and Technology, Daejeon, Republic of Korea.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31971030

Citation

Song, Mi-Kyung, et al. "Time-course Transcriptomic Alterations Reflect the Pathophysiology of Polyhexamethylene Guanidine Phosphate-induced Lung Injury in Rats." Inhalation Toxicology, vol. 31, no. 13-14, 2019, pp. 457-467.
Song MK, Kim DI, Lee K. Time-course transcriptomic alterations reflect the pathophysiology of polyhexamethylene guanidine phosphate-induced lung injury in rats. Inhal Toxicol. 2019;31(13-14):457-467.
Song, M. K., Kim, D. I., & Lee, K. (2019). Time-course transcriptomic alterations reflect the pathophysiology of polyhexamethylene guanidine phosphate-induced lung injury in rats. Inhalation Toxicology, 31(13-14), 457-467. https://doi.org/10.1080/08958378.2019.1707912
Song MK, Kim DI, Lee K. Time-course Transcriptomic Alterations Reflect the Pathophysiology of Polyhexamethylene Guanidine Phosphate-induced Lung Injury in Rats. Inhal Toxicol. 2019 Nov - Dec;31(13-14):457-467. PubMed PMID: 31971030.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Time-course transcriptomic alterations reflect the pathophysiology of polyhexamethylene guanidine phosphate-induced lung injury in rats. AU - Song,Mi-Kyung, AU - Kim,Dong Im, AU - Lee,Kyuhong, Y1 - 2020/01/23/ PY - 2020/1/24/pubmed PY - 2020/6/9/medline PY - 2020/1/24/entrez KW - Humidifier disinfectant KW - lung injury KW - pathophysiological change KW - polyhexamethylene guanidine phosphate (PHMG-P) KW - transcriptomic analysis SP - 457 EP - 467 JF - Inhalation toxicology JO - Inhal Toxicol VL - 31 IS - 13-14 N2 - Objective: Humidifier-disinfectant-induced lung injury is a new syndrome associated with a high mortality rate and characterized by severe hypersensitivity pneumonitis, acute interstitial pneumonia, or acute respiratory distress syndrome. Polyhexamethylene guanidine phosphate (PHMG-P), a guanidine-based antimicrobial agent, is a major component associated with severe lung injury. In-depth studies are needed to determine how PHMG-P affects pathogenesis at the molecular level. Therefore, in this study, we analyzed short-term (4 weeks) and long-term (10 weeks) PHMG-P-exposure-specific gene-expression patterns in rats to improve our understanding of time-dependent changes in fibrosis.Materials and methods: Gene-expression profiles were analyzed in rat lung tissues using DNA microarrays and bioinformatics tools.Results: Clustering analysis of gene-expression data showed different gene-alteration patterns in the short- and long-term exposure groups and higher sensitivity to gene-expression changes in the long-term exposure group than in the short-term exposure group. Supervised analysis revealed 34 short-term and 335 long-term exposure-specific genes, and functional analysis revealed that short-term exposure-specific genes were involved in PHMG-P-induced initial inflammatory responses, whereas long-term exposure-specific genes were involved in PHMG-P-related induction of chronic lung fibrosis.Conclusion: The results of transcriptomic analysis were consistent with lung histopathology results. These findings indicated that exposure-time-specific changes in gene expression closely reflected time-dependent pathological changes in PHMG-P-induced lung injury. SN - 1091-7691 UR - https://www.unboundmedicine.com/medline/citation/31971030/Time-course_transcriptomic_alterations_reflect_the_pathophysiology_of_polyhexamethylene_guanidine_phosphate-induced_lung_injury_in_rats L2 - http://www.tandfonline.com/doi/full/10.1080/08958378.2019.1707912 DB - PRIME DP - Unbound Medicine ER -