title: Epithelial-to-mesenchymal transition induced by Freund's adjuvant treatment in rat mesothelial cells: a morphological and immunocytochemical study.
abstract: Intraperitoneal injection of Freund's adjuvant induces acute peritonitis. By the time of the Freund's adjuvant treatment the flat, simple squamous epithelial cells became rounded, cuboidal shaped, many of them have lost their connection with the neighbouring cells and detached from the basement membrane. The macrophage markers' (ED1, OX43 and CD68) expression also increased in the mesothelial cells and more mesothelin and anti-ED1 double-labelled cells were found freely present close to the surface. The cytokeratin expression of the mesothelial cells has gradually decreased. At the 5th day of the inflammation practically there was no cytokeratin labelling present in the mesothelial cells and the mesothelin expression has significantly decreased. Parallel to this mesothelial cells started to express vimentin, a characteristic mesenchymal intermediate filament protein indicating that they gradually lost their epithelial character and gained mesenchymal phenotype. These results strongly suggest that under the effect of Freund's adjuvant treatment (inflammation) mesothelial cells can undergo epithelial-to-mesenchymal transition and differentiate into phagocytotic (macrophage-like) cells. Studying the caveolae/caveolin-1 on the plasma membrane of mesothelial cells we found that the Freund's adjuvant treatment has changed the cellular distribution of caveolin-1: as the inflammation progressed strong caveolin-1 labelling was found inside of the cytoplasm (in perinuclear localization) indicating that inflammation induced the caveolae internalization. These results indicate that caveolae/caveolin-1 might play important regulatory role in signal transduction leading to trasdifferentiation.
authors.affiliation: Department of Human Morphology and Developmental Biology, Semmelweis University Budapest, Tűzoltó u 58, Hungary. katzsanya@gmail.com
authors.forename: Sándor
authors.initials: S
authors.lastname: Katz
authors.forename: Petra
authors.initials: P
authors.lastname: Balogh
authors.forename: Nándor
authors.initials: N
authors.lastname: Nagy
authors.forename: Anna L
authors.initials: AL
authors.lastname: Kiss
mesh_terms: D000276:Adjuvants, Immunologic / Q000633:toxicity*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D051242:Caveolin 1 / Q000378:metabolism; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005620:Freund's Adjuvant / Q000633:toxicity*; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D007633:Keratins / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014746:Vimentin / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D015415:Biomarkers; D051242:Caveolin 1; D014746:Vimentin; D007633:Keratins; D005620:Freund's Adjuvant