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A Redox-Shifted Fibroblast Subpopulation Emerges in the Fibrotic Lung.

A Redox-Shifted Fibroblast Subpopulation Emerges in the Fibrotic Lung.

Authors :
Link, Patrick A.
Meridew, Jeffrey A.
Caporarello, Nunzia
Gao, Ashley Y.
Peters, Victor
Rojas, Mauricio
Tschumperlin, Daniel J.
Source :
American Journal of Respiratory Cell & Molecular Biology; Dec2024, Vol. 71 Issue 6, p718-729, 12p
Publication Year :
2024

Abstract

Idiopathic pulmonary fibrosis (IPF) is an aggressive and, thus far, incurable disease characterized by aberrant fibroblast-mediated extracellular matrix deposition. Our understanding of the disease etiology is incomplete; however, there is consensus that a reduction-oxidation (redox) imbalance plays a role. In this study, we use the autofluorescent properties of two redox molecules, NAD(P)H and FAD, to quantify changes in their relative abundance in living lung tissue of mice with experimental lung fibrosis and in freshly isolated cells from mouse lungs and humans with IPF. Our results identify cell population–specific intracellular redox changes in the lungs in experimental and human fibrosis. We focus particularly on redox changes within collagen-producing cells, where we identified a bimodal distribution of NAD(P)H concentrations, establishing NAD(P)H<superscript>high</superscript> and NAD(P)H<superscript>low</superscript> subpopulations. NAD(P)H<superscript>high</superscript> fibroblasts exhibited elevated profibrotic gene expression and decreased collagenolytic protease activity relative to NAD(P)H<superscript>low</superscript> fibroblasts. The NAD(P)H<superscript>high</superscript> population was present in healthy lungs but expanded with time after bleomycin injury, suggesting a potential role in fibrosis progression. We identified a similar increased abundance of NAD(P)H<superscript>high</superscript> cells in freshly dissociated lungs of subjects with IPF relative to control subjects, as well as similar reductions in collagenolytic activity in this cell population. These data highlight the complexity of redox state changes in experimental and human pulmonary fibrosis and the need for selective approaches to restore redox imbalances in the fibrotic lung. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
10441549
Volume :
71
Issue :
6
Database :
Complementary Index
Journal :
American Journal of Respiratory Cell & Molecular Biology
Publication Type :
Academic Journal
Accession number :
181135656
Full Text :
https://doi.org/10.1165/rcmb.2023-0346OC