Putting the brakes on age-related idiopathic pulmonary fibrosis: Can Nox4 inhibitors suppress IPF?

Turn, Christina S.; Lockey, Richard F.; Kolliputi, Narasaiah

doi:10.1016/j.exger.2015.02.002

Cited by 4 publications

(1 citation statement)

References 9 publications

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“…The two major sources of ROS in cells are from mitochondrial oxidative phosphorylation and activation of NADPH oxidases (NOXs) [ 202 , 203 ]. Altered mitochondrial homeostasis that includes increased mitochondrial ROS (mtROS), impaired respiration, mtDNA damage, compromised mitochondrial dynamics and mitophagy have been reported in epithelial cells and fibroblasts from healthy aged lungs, IPF lungs and lungs from murine models of bleomycin- and asbestos-induced PF, resulting from upregulation of NADPH Oxidase (NOX) 4, and increased mtROS and mtDNA damage [ 204 , 205 , 206 , 207 ]. TGF-β has been shown to induce mtROS through decreased Complex IV activity in senescent cells [ 208 , 209 ], and recent studies suggest that SPHK1/S1P signaling stimulates NOX2-dependent ROS generation in lung endothelial cells [ 137 , 210 , 211 , 212 ], and mtROS in lung fibroblasts [ 158 ].…”

Section: Sphingolipids Sphingolipid Metabolizing Enzymes and S1pmentioning

confidence: 99%

Lipid Mediators Regulate Pulmonary Fibrosis: Potential Mechanisms and Signaling Pathways

Suryadevara

Ramchandran

Kamp

et al. 2020

IJMS

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Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease of unknown etiology characterized by distorted distal lung architecture, inflammation, and fibrosis. The molecular mechanisms involved in the pathophysiology of IPF are incompletely defined. Several lung cell types including alveolar epithelial cells, fibroblasts, monocyte-derived macrophages, and endothelial cells have been implicated in the development and progression of fibrosis. Regardless of the cell types involved, changes in gene expression, disrupted glycolysis, and mitochondrial oxidation, dysregulated protein folding, and altered phospholipid and sphingolipid metabolism result in activation of myofibroblast, deposition of extracellular matrix proteins, remodeling of lung architecture and fibrosis. Lipid mediators derived from phospholipids, sphingolipids, and polyunsaturated fatty acids play an important role in the pathogenesis of pulmonary fibrosis and have been described to exhibit pro- and anti-fibrotic effects in IPF and in preclinical animal models of lung fibrosis. This review describes the current understanding of the role and signaling pathways of prostanoids, lysophospholipids, and sphingolipids and their metabolizing enzymes in the development of lung fibrosis. Further, several of the lipid mediators and enzymes involved in their metabolism are therapeutic targets for drug development to treat IPF.

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Section: Sphingolipids Sphingolipid Metabolizing Enzymes and S1pmentioning

confidence: 99%

Lipid Mediators Regulate Pulmonary Fibrosis: Potential Mechanisms and Signaling Pathways

Suryadevara

Ramchandran

Kamp

et al. 2020

IJMS

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Emerging Therapeutic Targets and Therapies in Idiopathic Pulmonary Fibrosis

Parvathaneni

Shukla

Gupta

2018

Molecular and Translational Medicine

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The Role of Aging in Idiopathic Pulmonary Fibrosis

Leung

Cho

Lockey

et al. 2015

Lung

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Idiopathic pulmonary fibrosis (IPF) has been gathering interest in recent years and as such this review will focus on the potential contributions that age plays on its onset and prevalence. Environmental stress over time caused by the inhalation of foreign substances results in subsequent damage and repair of lung tissue. This damage prematurely causes a decrease in stem cell differentiation potential. In conjunction with declining proliferation, the correlation between age and general attenuation of the immune system allows for the introduction of viral components such as the Epstein-Barr virus which has been associated with lung injury, a causation which has not yet been investigated. But, regardless of environmental factors, cellular alterations due to, or in correlation with, age could result in the onset or prolonging of IPF. General genetic mutation and epigenetic methylations accumulate over a person's lifespan while miRNA expression changes from birth to adulthood. This collection of alterations over time may cause dysregulation of expressed genetic material which can result in many age-related diseases including pulmonary fibrosis. Such alterations would be prevented by autophagy or cell-mediated apoptosis, but due to age-related dysregulations, these systems function at a diminished capacity. On the cellular level, the end result is an accumulation of dysfunctional organelles with damaged molecules, such as reactive oxygen species, and general genetic and epigenetic alterations resulting in excess generation of fibrous tissue and overall damage to the pulmonary system.

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Putting the brakes on age-related idiopathic pulmonary fibrosis: Can Nox4 inhibitors suppress IPF?

Cited by 4 publications

References 9 publications

Lipid Mediators Regulate Pulmonary Fibrosis: Potential Mechanisms and Signaling Pathways

Lipid Mediators Regulate Pulmonary Fibrosis: Potential Mechanisms and Signaling Pathways

Emerging Therapeutic Targets and Therapies in Idiopathic Pulmonary Fibrosis

The Role of Aging in Idiopathic Pulmonary Fibrosis

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