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Research Paper|Volume 8, Issue 11|pp 3091—3109

The role of club cell phenoconversion and migration in idiopathic pulmonary fibrosis

Jutaro Fukumoto1, Ramani Soundararajan1, Joseph Leung1, Ruan Cox Jr.1,2, Sanjay Mahendrasah1, Neha Muthavarapu1, Travis Herrin1, Alexander Czachor1, Lee C. Tan1, Nima Hosseinian1, Priyanshi Patel1, Jayanthraj Gone1, Mason T. Breitzig1, Young Cho1, Andrew J. Cooke1, Lakshmi Galam1, Venkata Ramireddy Narala1,4, Yashwant Pathak3, Richard F. Lockey1, Narasaiah Kolliputi1,2
  • 1Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA
  • 2Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA
  • 3College of Pharmacy, University of South Florida, Tampa, FL 33612, USA
  • 4Department of Zoology, Yogi Vemana University, Kadapa, AP 516003, India
Received: August 7, 2016Accepted: November 7, 2016Published: November 29, 2016

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.