The Role of Club Cell Phenoconversion and Migration in Idiopathic Pulmonary Fibrosis

Authors

Jutaro Fukumoto, University of South FloridaFollow
Ramani Soundararajan, University of South FloridaFollow
Joseph Leung, University of South Florida
Ruan Cox Jr., University of South Florida
Sanjay Mahendrasah, University of South Florida
Neha Muthavarapu, University of South Florida
Travis Herrin, University of South Florida
Alexander Czachor, University of South Florida
Lee C. Tan, University of South Florida
Nima Hosseinian, University of South Florida
Priyanshi Patel, University of South Florida
Jayanthraj Gone, University of South Florida
Mason T. Breitzig, University of South Florida
Young Cho, University of South Florida
Andrew J. Cooke, University of South Florida
Lakshmi Galam, University of South FloridaFollow
Venkata Ramireddy Narala, University of South Florida
Yashwant Pathak, University of South FloridaFollow
Richard F. Lockey, University of South FloridaFollow
Narasaiah Kolliputi, University of South FloridaFollow

Document Type

Article

Publication Date

2016

Digital Object Identifier (DOI)

https://doi.org/10.18632/aging.101115

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.

Was this content written or created while at USF?

Yes

Citation / Publisher Attribution

Aging, v. 8, issue 11, p. 3091-3109

Scholar Commons Citation

Fukumoto, Jutaro; Soundararajan, Ramani; Leung, Joseph; Cox, Ruan Jr.; Mahendrasah, Sanjay; Muthavarapu, Neha; Herrin, Travis; Czachor, Alexander; Tan, Lee C.; Hosseinian, Nima; Patel, Priyanshi; Gone, Jayanthraj; Breitzig, Mason T.; Cho, Young; Cooke, Andrew J.; Galam, Lakshmi; Narala, Venkata Ramireddy; Pathak, Yashwant; Lockey, Richard F.; and Kolliputi, Narasaiah, "The Role of Club Cell Phenoconversion and Migration in Idiopathic Pulmonary Fibrosis" (2016). Internal Medicine Faculty Publications. 206.
https://digitalcommons.usf.edu/intmed_facpub/206