title: Epithelial to mesenchymal transition-related proteins ZEB1, β-catenin, and β-tubulin-III in idiopathic pulmonary fibrosis.
abstract: Epithelial to mesenchymal transition has been suggested as a relevant contributor to pulmonary fibrosis, but how and where this complex process is triggered in idiopathic pulmonary fibrosis is not fully understood. Beta-tubulin-III (Tubβ3), ZEB1, and β-catenin are partially under the negative control of miR-200, a family of micro-RNAs playing a major role in epithelial to mesenchymal transition, that are reduced in experimental lung fibrosis and idiopathic pulmonary fibrosis. We wonder whether in situ expression of these proteins is increased in idiopathic pulmonary fibrosis, to better understand the significance of miR-200 feedback loop and epithelial to mesenchymal transition. We investigated the immunohistochemical and immunofluorescent expression and precise location of ZEB1, Tubβ3, and β-catenin in tissue samples from 34 idiopathic pulmonary fibrosis cases and 21 controls (5 normal lungs and 16 other interstitial lung diseases). In 100% idiopathic pulmonary fibrosis samples, the three proteins were concurrently expressed in fibroblastic foci, as well in damaged epithelial cells overlying these lesions and in pericytes within neo-angiogenesis areas. These results were also confirmed by immunofluorescence assay. In controls the abnormal expression of the three proteins was absent or limited. This is the first study that relates concurrent expression of Tubβ3, ZEB1, and β-catenin to abnormal epithelial and myofibroblast differentiation in idiopathic pulmonary fibrosis, providing indirect but robust evidence of miR-200 deregulation and epithelial to mesenchymal transition activation in idiopathic pulmonary fibrosis. The abnormal expression and localization of these proteins in bronchiolar fibro-proliferative lesions are unique for idiopathic pulmonary fibrosis, and might represent a disease-specific marker in challenging lung biopsies.
authors: Anatomic Pathology, University and Hospital Trust, Verona, Italy.
authors: Marco
authors: M
authors: Chilosi
authors: Anatomic Pathology, University and Hospital Trust, Verona, Italy.
authors: Anna
authors: A
authors: Caliò
authors: Pulmonary Division, University and Hospital Trust, Verona, Italy.
authors: Andrea
authors: A
authors: Rossi
authors: Anatomic Pathology, University and Hospital Trust, Verona, Italy.
authors: Eliana
authors: E
authors: Gilioli
authors: Anatomic Pathology, University and Hospital Trust, Verona, Italy.|Department of Pathology, IRCSS San Raffaele Scientific Institute, Milan, Italy.
authors: Federica
authors: F
authors: Pedica
authors: Anatomic Pathology, University and Hospital Trust, Verona, Italy.
authors: Licia
authors: L
authors: Montagna
authors: Anatomic Pathology, University and Hospital Trust, Verona, Italy.
authors: Serena
authors: S
authors: Pedron
authors: Department of Pulmonology, University Hospital of Cattinara, Trieste, Italy.
authors: Marco
authors: M
authors: Confalonieri
authors: Department of Pathology, IRCSS San Raffaele Scientific Institute, Milan, Italy.
authors: Claudio
authors: C
authors: Doglioni
authors: Department of Pulmonary Medicine, Department of Medicine-II University of Wien, Vienna, Austria.
authors: Rolf
authors: R
authors: Ziesche
authors: Department of Medicine I, Institute of Cancer Research, Medical University of Wien, Austria.
authors: Markus
authors: M
authors: Grubinger
authors: Department of Medicine I, Institute of Cancer Research, Medical University of Wien, Austria.
authors: Wolfgang
authors: W
authors: Mikulits
authors: Pulmonology Unit, Department of Thoracic Diseases, GB Morgagni-L Pierantoni Hospital, Forlì, Italy.|Department of Respiratory Diseases and Allergology, Aarhus University Hospital, Aarhus, Denmark.
authors: Venerino
authors: V
authors: Poletti
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000378:metabolism*; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000378:metabolism*; D058628:Myofibroblasts / Q000378:metabolism / Q000473:pathology; D014404:Tubulin / Q000378:metabolism*; D000071799:Zinc Finger E-box-Binding Homeobox 1 / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D014404:Tubulin; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; D051176:beta Catenin