Journal article
Transcriptome sequencing of 3,3′,4,4′,5-Pentachlorobiphenyl (PCB126)-treated human preadipocytes demonstrates progressive changes in pathways associated with inflammation and diabetes
Toxicology in vitro, Vol.83, 105396
09/2022
DOI: 10.1016/j.tiv.2022.105396
PMCID: PMC9423686
PMID: 35618242
Abstract
Polychlorinated biphenyls (PCBs) are persistent organic pollutants that accumulate in adipose tissue and have been associated with cardiometabolic disease. We have previously demonstrated that exposure of human preadipocytes to the dioxin-like PCB126 disrupts adipogenesis via the aryl hydrocarbon receptor (AhR). To further understand how PCB126 disrupts adipose tissue cells, we performed RNAseq analysis of PCB126-treated human preadipocytes over a 3-day time course. The most significant predicted upstream regulator affected by PCB126 exposure at the early time point of 9 h was the AhR. Progressive changes occurred in the number and magnitude of transcript levels of genes associated with inflammation, most closely fitting the pathways of cytokine-cytokine-receptor signaling and the AGE-RAGE diabetic complications pathway. Transcript levels of genes involved in the IL-17A, IL-1β, MAP kinase, and NF-κB signaling pathways were increasingly dysregulated by PCB126 over time. Our results illustrate the progressive time-dependent nature of transcriptional changes caused by toxicants such as PCB126, point to important pathways affected by PCB126 exposure, and provide a rich dataset for further studies to address how PCB126 and other AhR agonists disrupt preadipocyte function. These findings have implications for understanding how dioxin-like PCBs and other dioxin-like compounds are involved in the development of obesity and diabetes.
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•RNAseq studies on PCB126-treated human preadipocytes over a time course demonstrated progressive changes in the number and magnitude of transcript genes associated with the aryl hydrocarbon receptor (AhR) and cytokine-cytokine-receptor signaling, including the IL-17A and IL-1β pathways.•The AGE-RAGE (advanced glycation endproducts-receptor for advanced glycation endproducts) diabetic complications pathway, a pathway known to be important in the development of metabolic syndrome, was also activated by PCB126 in human preadipocytes.•Our results illustrate the progressive time-dependent nature of transcriptional changes caused by toxicants such as PCB126, point to important pathways affected by PCB126 exposure, and provide a rich data-set for further studies to address how PCB126 and other AhR agonists disrupt preadipocyte function to cause cardiometabolic disease.
Details
- Title: Subtitle
- Transcriptome sequencing of 3,3′,4,4′,5-Pentachlorobiphenyl (PCB126)-treated human preadipocytes demonstrates progressive changes in pathways associated with inflammation and diabetes
- Creators
- Francoise A. Gourronc - University of IowaBrynn K. Helm - University of IowaLarry W. Robertson - University of IowaMichael S. Chimenti - University of IowaHans Joachim-Lehmler - University of IowaJames A. Ankrum - University of IowaAloysius J. Klingelhutz - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Toxicology in vitro, Vol.83, 105396
- DOI
- 10.1016/j.tiv.2022.105396
- PMID
- 35618242
- PMCID
- PMC9423686
- NLM abbreviation
- Toxicol In Vitro
- ISSN
- 0887-2333
- eISSN
- 1879-3177
- Publisher
- Elsevier Ltd
- Language
- English
- Electronic publication date
- 05/23/2022
- Date published
- 09/2022
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Microbiology and Immunology; Occupational and Environmental Health; Iowa Neuroscience Institute; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Iowa Superfund Research Program; Iowa Institute of Human Genetics
- Record Identifier
- 9984259620302771
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