title: The role of club cell phenoconversion and migration in idiopathic pulmonary fibrosis.
abstract: Idiopathic pulmonary fibrosis (IPF) is an age-related multifactorial disease featuring non-uniform lung fibrosis. The decisive cellular events at early stages of IPF are poorly understood. While the involvement of club cells in IPF pathogenesis is unclear, their migration has been associated with lung fibrosis. In this study, we labeled club cells immunohistochemically in IPF lungs using a club cell marker Claudin-10 (Cldn10), a unique protein based on the recent report which demonstrated that the appearance of Cldn10 in developing and repairing lungs precedes other club cell markers including club cell secretory protein (CCSP). Cldn10-positive cells in IPF lungs displayed marked pleomorphism and were found in varied arrangements, suggesting their phenoconversion. These results were corroborated by immunogold labeling for Cldn10. Further, immunohistochemical double-labeling for Cldn10 and α-smooth muscle actin (α-SMA) demonstrated that aberrant α-SMA signals are frequently encountered near disorganized Cldn10-positive cells in hyperplastic bronchiolar epithelium and thickened interstitium of IPF lungs. Collectively, these data indicate that club cells actively participate in the initiation and progression of IPF through phenoconversion involving the acquisition of proliferative and migratory abilities. Thus, our new findings open the possibility for club cell-targeted therapy to become a strategic option for the treatment of IPF.
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Jutaro
authors.initials: J
authors.lastname: Fukumoto
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Ramani
authors.initials: R
authors.lastname: Soundararajan
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Leung
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.|Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Ruan
authors.initials: R
authors.lastname: Cox
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Mahendrasah
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Neha
authors.initials: N
authors.lastname: Muthavarapu
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Travis
authors.initials: T
authors.lastname: Herrin
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Czachor
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Lee C
authors.initials: LC
authors.lastname: Tan
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Nima
authors.initials: N
authors.lastname: Hosseinian
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Priyanshi
authors.initials: P
authors.lastname: Patel
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Jayanthraj
authors.initials: J
authors.lastname: Gone
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Mason T
authors.initials: MT
authors.lastname: Breitzig
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Young
authors.initials: Y
authors.lastname: Cho
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Cooke
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Galam
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.|Department of Zoology, Yogi Vemana University, Kadapa, AP 516003, India.
authors.forename: Venkata Ramireddy
authors.initials: VR
authors.lastname: Narala
authors.affiliation: College of Pharmacy, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Yashwant
authors.initials: Y
authors.lastname: Pathak
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Lockey
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.|Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Narasaiah
authors.initials: N
authors.lastname: Kolliputi
mesh_terms: D000199:Actins / Q000378:metabolism*; D056809:Alveolar Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D002465:Cell Movement; D057167:Claudins / Q000378:metabolism*; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism / Q000473:pathology
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D057167:Claudins; C502009:claudin 10
keywords: Claudin10/Cldn10/Claudin-10; club cell secretory protein (CCSP); club cells; idiopathic pulmonary fibrosis (IPF); migration