Author ORCID Identifier
https://orcid.org/0000-0001-5876-8256
Date Available
5-15-2026
Year of Publication
2025
Document Type
Doctoral Dissertation
Degree Name
Doctor of Philosophy (PhD)
College
Medicine
Department/School/Program
Toxicology and Cancer Biology
Faculty
David Orren, advisor
Faculty
Isabel Mellon, DGS
Abstract
Cigarette smoke contains over 7,000 chemicals, many being carcinogens and proinflammatory agents contributing to chronic respiratory diseases like COPD and lung cancer. This study investigated responses of human bronchial epithelial cells (HBECs) to cigarette smoke condensate (CSC), focusing on oxidative stress and NF-κB signaling. Three HBEC lines were exposed to non-cytotoxic CSC doses for 48 hours, inducing morphological changes consistent with epithelial-to-mesenchymal transition (EMT). RNA sequencing revealed transcriptomic shifts in all cell lines, particularly affecting genes related to oxidative stress, inflammation, hypoxia, and metabolism. Enrichment analyses confirmed activation of NRF2 antioxidant, NF-κB and IL-17 inflammatory, and hypoxiainducible factor pathways, indicating a coordinated stress response. Protein analyses confirmed increased phosphorylated NF-κB p65 expression in CSCtreated HBEC3KT cells. Scratch wound assays demonstrated enhanced migratory ability following CSC exposure, while decreases in E-cadherin and increases in vimentin supported partial EMT induction. Cell viability assays showed moderate cytotoxicity after 48-hour CSC treatment, with HBEC2 being most sensitive. Results suggest a state of chronic cellular stress, inflammation, and hypoxia with impaired epithelial restitution—hallmarks of early airway remodeling in smoke-related lung pathologies. This integrated analysis provides mechanistic insights into early events driving airway injury in smokers and may inform therapeutic strategies targeting epithelial resilience.
Digital Object Identifier (DOI)
https://doi.org/10.13023/etd.2025.215
Funding Information
Food and Drug Administration (FDA), grants UC2FD005049 and UC2FD005671
Recommended Citation
Alqithami, Sarah M., "NF-κB-Mediated Oxidative Stress Drives Cigarette Smoke-Induced EMT in Human Bronchial Cells" (2025). Theses and Dissertations--Toxicology and Cancer Biology. 62.
https://uknowledge.uky.edu/toxicology_etds/62
