Events Calendar

Molecular Toxicology Journal Club

EOH student Alexander Schuyler will present the article

"Genome-Wide Analysis Reveals Mucociliary Remodeling of the Nasal Airway Epithelium Induced by Urban PM2.5"

Montgomery MT, Sajuthi SP, Cho SH, Everman JL, Rios CL, Goldfarbmuren KC, Jackson ND, Saef B, Cromie M, Eng C, Medina V, Elhawary JR, Oh SS, Rodriguez-Santana J, Vladar EK, Burchard EG, Seibold MA

Abstract

Air pollution particulate matter <2.5 μm (PM2.5) exposure is associated with poor respiratory outcomes. Mechanisms underlying PM2.5-induced lung pathobiology are poorly understood but likely involve cellular and molecular changes to the airway epithelium. We extracted and chemically characterized the organic and water-soluble components of air pollution PM2.5 samples, then determined the whole transcriptome response of human nasal mucociliary airway epithelial cultures to a dose series of PM2.5 extracts. We found that PM2.5 organic extract (OE), but not water-soluble extract, elicited a potent, dose-dependent transcriptomic response from the mucociliary epithelium. Exposure to a moderate OE dose modified the expression of 424 genes, including activation of aryl hydrocarbon receptor signaling and an IL-1 inflammatory program. We generated an OE-response gene network defined by eight functional enrichment groups, which exhibited high connectivity through CYP1A1, IL1A, and IL1B. This OE exposure also robustly activated a mucus secretory expression program (>100 genes), which included transcriptional drivers of mucus metaplasia (SPDEF and FOXA3). Exposure to a higher OE dose modified the expression of 1,240 genes and further exacerbated expression responses observed at the moderate dose, including the mucus secretory program. Moreover, the higher OE dose significantly increased the MUC5AC/MUC5B gel-forming mucin expression ratio and strongly downregulated ciliated cell expression programs, including key ciliating cell transcription factors (e.g., FOXJ1 and MCIDAS). Chronic OE stimulation induced mucus metaplasia-like remodeling characterized by increases in MUC5AC+ secretory cells and MUC5AC mucus secretions. This epithelial remodeling may underlie poor respiratory outcomes associated with high PM2.5 exposure.

PLEASE SUPPORT OUR STUDENT PRESENTERS

Organized by Dr. Nicholas Fitz of the Department of Environmental and Occupational Health, this weekly course is designed to expose EOH students to the newest and most exciting research in a diverse set of topics related to toxicology.  Guests are welcome.

Dial-In Information

Contact Dr. Nicholas Fitz (nffitz@pitt.edu) for Zoom information to attend.

Thursday, November 5 at 11:00 a.m.

Virtual Event

Molecular Toxicology Journal Club

EOH student Alexander Schuyler will present the article

"Genome-Wide Analysis Reveals Mucociliary Remodeling of the Nasal Airway Epithelium Induced by Urban PM2.5"

Montgomery MT, Sajuthi SP, Cho SH, Everman JL, Rios CL, Goldfarbmuren KC, Jackson ND, Saef B, Cromie M, Eng C, Medina V, Elhawary JR, Oh SS, Rodriguez-Santana J, Vladar EK, Burchard EG, Seibold MA

Abstract

Air pollution particulate matter <2.5 μm (PM2.5) exposure is associated with poor respiratory outcomes. Mechanisms underlying PM2.5-induced lung pathobiology are poorly understood but likely involve cellular and molecular changes to the airway epithelium. We extracted and chemically characterized the organic and water-soluble components of air pollution PM2.5 samples, then determined the whole transcriptome response of human nasal mucociliary airway epithelial cultures to a dose series of PM2.5 extracts. We found that PM2.5 organic extract (OE), but not water-soluble extract, elicited a potent, dose-dependent transcriptomic response from the mucociliary epithelium. Exposure to a moderate OE dose modified the expression of 424 genes, including activation of aryl hydrocarbon receptor signaling and an IL-1 inflammatory program. We generated an OE-response gene network defined by eight functional enrichment groups, which exhibited high connectivity through CYP1A1, IL1A, and IL1B. This OE exposure also robustly activated a mucus secretory expression program (>100 genes), which included transcriptional drivers of mucus metaplasia (SPDEF and FOXA3). Exposure to a higher OE dose modified the expression of 1,240 genes and further exacerbated expression responses observed at the moderate dose, including the mucus secretory program. Moreover, the higher OE dose significantly increased the MUC5AC/MUC5B gel-forming mucin expression ratio and strongly downregulated ciliated cell expression programs, including key ciliating cell transcription factors (e.g., FOXJ1 and MCIDAS). Chronic OE stimulation induced mucus metaplasia-like remodeling characterized by increases in MUC5AC+ secretory cells and MUC5AC mucus secretions. This epithelial remodeling may underlie poor respiratory outcomes associated with high PM2.5 exposure.

PLEASE SUPPORT OUR STUDENT PRESENTERS

Organized by Dr. Nicholas Fitz of the Department of Environmental and Occupational Health, this weekly course is designed to expose EOH students to the newest and most exciting research in a diverse set of topics related to toxicology.  Guests are welcome.

Dial-In Information

Contact Dr. Nicholas Fitz (nffitz@pitt.edu) for Zoom information to attend.

Thursday, November 5 at 11:00 a.m.

Virtual Event

Event Type

Virtual

Topic

Research