Oxidative Stress Induces Club Cell Proliferation and Pulmonary Fibrosis in Atp8b1 Mutant Mice

Authors

Jutaro Fukumoto, University of South FloridaFollow
Joseph Leung, University of South Florida
Ruan Cox Jr, University of South Florida
Alexander Czachor, University of South Florida
Prasanna Tamarapu Parthasarathy, University of South Florida
Venu Lagishetty, University of South Florida
Maria Mandry, University of South Florida
Nima Hosseinian, University of South Florida
Priyanshi Patel, University of South Florida
Brittany Perry, University of South Florida
Mason T. Breitzig, University of South Florida
Matthew Alleyn, University of South Florida
Athena Failla, University of South Florida
Young Cho, University of South Florida
Andrew J. Cooke, University of South Florida
Lakshmi Galam, University of South FloridaFollow
Ramani Soundararajan, University of South FloridaFollow
Nirmal Sharma, University of South Florida
Richard F. Lockey, University of South FloridaFollow
Narasaiah Kolliputi, University of South FloridaFollow

Document Type

Article

Publication Date

2018

Digital Object Identifier (DOI)

https://doi.org/10.18632/aging.101742

Abstract

Atp8b1 (ATPase, aminophospholipid transporter, class I, type 8B, member 1) is a cardiolipin transporter in the apical membrane of lung epithelial cells. While the role of Atp8b1 in pneumonia-induced acute lung injury (ALI) has been well studied, its potential role in oxidative stress-induced ALI is poorly understood. We herein show that Atp8b1G308V/G308V mice under hyperoxic conditions display exacerbated cell apoptosis at alveolar epithelium and aberrant proliferation of club cells at bronchiolar epithelium. This hyperoxia-induced ambivalent response in Atp8b1G308V/G308V lungs was followed by patchy distribution of non-uniform interstitial fibrosis at late recovery phase under normoxia. Since this club cell abnormality is commonly observed between Atp8b1G308V/G308V lungs under hyperoxic conditions and IPF lungs, we characterized this mouse fibrosis model focusing on club cells. Intriguingly, subcellular morphological analysis of IPF lungs, using transmission electron microscopy (TEM), revealed that metaplastic bronchiolar epithelial cells in fibrotic lesions and deformed type II alveolar epithelial cells (AECs) in alveoli with mild fibrosis, have common morphological features including cytoplasmic vacuolation and dysmorphic lamellar bodies. In conclusion, the combination of Atp8b1 mutation and hyperoxic insult serves as a novel platform to study unfocused role of club cells in IPF.

Rights Information

This work is licensed under a Creative Commons Attribution 3.0 License.

Was this content written or created while at USF?

Yes

Citation / Publisher Attribution

Aging, v. 11, issue 1, p. 209-229

Scholar Commons Citation

Fukumoto, Jutaro; Leung, Joseph; Cox, Ruan Jr; Czachor, Alexander; Parthasarathy, Prasanna Tamarapu; Lagishetty, Venu; Mandry, Maria; Hosseinian, Nima; Patel, Priyanshi; Perry, Brittany; Breitzig, Mason T.; Alleyn, Matthew; Failla, Athena; Cho, Young; Cooke, Andrew J.; Galam, Lakshmi; Soundararajan, Ramani; Sharma, Nirmal; Lockey, Richard F.; and Kolliputi, Narasaiah, "Oxidative Stress Induces Club Cell Proliferation and Pulmonary Fibrosis in Atp8b1 Mutant Mice" (2018). Molecular Medicine Faculty Publications. 54.
https://digitalcommons.usf.edu/mme_facpub/54