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Pioglitazone is a peroxisome proliferator\u2010activated receptor \u03b3 (PPAR\u03b3) agonist shown to prevent lung tumors in preclinical models. We investigated pioglitazone's effect on lesion development and markers of potential preventive mechanisms in the NTCU model. Female FVB\/N mice were exposed to vehicle, NTCU or NTCU + oral pioglitazone for 32\u2009weeks. NTCU induces the appearance of basal cells in murine airways while decreasing\/changing their epithelial cell makeup, resulting in development of bronchial dysplasia. H&amp;E and keratin 5 (KRT5) staining were used to detect and grade squamous lesions in formalin fixed lungs. mRNA expression of epithelial to mesenchymal transition (EMT) markers and basal cell markers were measured by qPCR. Dysplasia persistence markers desmoglein 3 and polo like kinase 1 were measured by immunohistochemistry. Basal cell markers KRT14 and p63, club cell specific protein and ciliated cell marker acetylated tubulin were measured by immunofluorescence. Pioglitazone treatment significantly reduced squamous lesions and the presence of airway basal cells, along with increasing normal epithelial cells in the airways of NTCU\u2010exposed mice. Pioglitazone also significantly influenced EMT gene expression to promote a more epithelial, and less mesenchymal, phenotype. Pioglitazone reduced the presence of squamous dysplasia and maintained normal airway cell composition. This work increases the knowledge of mechanistic pathways in PPAR\u03b3 agonism for lung cancer interception and provides a basis for further investigation to advance this chemoprevention strategy.<\/jats:p>","DOI":"10.1002\/ijc.34210","type":"journal-article","created":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T15:53:05Z","timestamp":1657727585000},"page":"2195-2205","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["<scp>PPARgamma<\/scp> agonism inhibits progression of premalignant lesions in a murine lung squamous cell carcinoma model"],"prefix":"10.1002","volume":"151","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9224-3648","authenticated-orcid":false,"given":"Lori D.","family":"Dwyer\u2010Nield","sequence":"first","affiliation":[{"name":"Skaggs School of Pharmacy University of Colorado Anschutz Medical Campus  Aurora Colorado 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