title: Endothelial and Epithelial Cell Transition to a Mesenchymal Phenotype Was Delineated by Nestin Expression.
abstract: Endothelial and epithelial cell transition to a mesenchymal phenotype was identified as cellular paradigms implicated in the appearance of fibroblasts and development of reactive fibrosis in interstitial lung disease. The intermediate filament protein nestin was highly expressed in fibrotic tissue, detected in fibroblasts and participated in proliferation and migration. The present study tested the hypothesis that the transition of endothelial and epithelial cells to a mesenchymal phenotype was delineated by nestin expression. Three weeks following hypobaric hypoxia, adult male Sprague-Dawley rats characterized by alveolar and perivascular lung fibrosis were associated with increased nestin protein and mRNA levels and marked appearance of nestin/collagen type I((+))-fibroblasts. In the perivascular region of hypobaric hypoxic rats, displaced CD31((+))-endothelial cells were detected, exhibited a mesenchymal phenotype and co-expressed nestin. Likewise, epithelial cells in the lungs of hypobaric hypoxic rats transitioned to a mesenchymal phenotype distinguished by the co-expression of E-cadherin and collagen. Following the removal of FBS from primary passage rat alveolar epithelial cells, TGF-β1 was detected in the media and a subpopulation acquired a mesenchymal phenotype characterized by E-cadherin downregulation and concomitant induction of collagen and nestin. Bone morphogenic protein-7 treatment of alveolar epithelial cells prevented E-cadherin downregulation, suppressed collagen induction but partially inhibited nestin expression. These data support the premise that the transition of endothelial and epithelial cells to a mesenchymal cell may have contributed in part to the appearance nestin/collagen type I((+))-fibroblasts and the reactive fibrotic response in the lungs of hypobaric hypoxic rats.
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montréal, Québec, Canada.|Département de Physiologie Moléculaire et Intégrative, Université de Montréal, Montréal, Quebéc, Canada.
authors.forename: Andréanne
authors.initials: A
authors.lastname: Chabot
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montréal, Québec, Canada.|Département de Physiologie Moléculaire et Intégrative, Université de Montréal, Montréal, Quebéc, Canada.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Hertig
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Elena
authors.initials: E
authors.lastname: Boscher
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Quang Trinh
authors.initials: QT
authors.lastname: Nguyen
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montréal, Québec, Canada.|Département de Biochimie et, Montréal, Québec, Canada.|Médecine, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Benoît
authors.initials: B
authors.lastname: Boivin
authors.affiliation: CRCHUM, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Jasmine
authors.initials: J
authors.lastname: Chebli
authors.affiliation: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Département de Médicine, Université Laval, Québec, Canada.
authors.forename: Lyse
authors.initials: L
authors.lastname: Bissonnette
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Louis
authors.initials: L
authors.lastname: Villeneuve
authors.affiliation: CRCHUM, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Brochiero
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montréal, Québec, Canada.|Médecine, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Dupuis
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montréal, Québec, Canada.|Département de Physiologie Moléculaire et Intégrative, Université de Montréal, Montréal, Quebéc, Canada.
authors.forename: Angelino
authors.initials: A
authors.lastname: Calderone
mesh_terms: D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000008:administration & dosage; D015820:Cadherins / Q000096:biosynthesis; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D024042:Collagen Type I / Q000096:biosynthesis / Q000235:genetics; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005347:Fibroblasts; D005786:Gene Expression Regulation / Q000187:drug effects; D000860:Hypoxia / Q000235:genetics* / Q000473:pathology; D064231:Nestin / Q000096:biosynthesis* / Q000235:genetics; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D053773:Transforming Growth Factor beta1
chemical_list: D055419:Bone Morphogenetic Protein 7; D015820:Cadherins; D024042:Collagen Type I; C577486:Nes protein, rat; D064231:Nestin; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1