Targeting the isoprenoid pathway to abrogate progression of pulmonary fibrosis.

@article{OsbornHeaford2015TargetingTI,
  title={Targeting the isoprenoid pathway to abrogate progression of pulmonary fibrosis.},
  author={Heather L Osborn-Heaford and Shubha Murthy and Linlin Gu and Jennifer L. Larson-Casey and Alan J Ryan and Lei Shi and Michael Glogauer and Jeffrey D Neighbors and Raymond J. Hohl and A. Brent Carter},
  journal={Free radical biology \& medicine},
  year={2015},
  volume={86},
  pages={
          47-56
        }
}

Figures from this paper

Oxidative Stress in Pulmonary Fibrosis.

TLDR
This article discusses cellular sources of oxidant production, and antioxidant defenses, both enzymatic and nonenzymatic, and links oxidative stress to the biology of aging that involves DNA damage responses, loss of proteostasis, and mitochondrial dysfunction.

Macrophages utilize the mitochondrial calcium uniporter for profibrotic polarization

TLDR
Regulation of mitochondrial Ca2+ suggests that MCU may play a pivotal role in the development of fibrosis and could potentially be a therapeutic target for pulmonary fibrosis.

F 2-isoprostanes can mediate bleomycin-induced lung fibrosis

TLDR
Evidence of a profibrotic role for these mediators in the pathogenesis of pulmonary fibrosis is provided by providing evidence of the presence of the thromboxane A⁠ 2 receptor (TP receptor) on lung fibroblasts and suggested that the observed effects may be elicited through the binding to this receptor.

Macrophages: friend or foe in idiopathic pulmonary fibrosis?

TLDR
The goal is to update the understanding of the mechanisms underlying the initiation and progression of IPF, and by which, it expects to provide help for developing effective therapeutic strategies in clinical settings.

Molecular hydrogen is a promising therapeutic agent for pulmonary disease

TLDR
This review highlights the multiple functions of hydrogen and the mechanisms underlying its protective effects in various lung diseases, with a focus on its roles in disease pathogenesis and clinical significance.

References

SHOWING 1-10 OF 65 REFERENCES

Modulation of reactive oxygen species by Rac1 or catalase prevents asbestos-induced pulmonary fibrosis.

TLDR
It is demonstrated that Rac1 null mice are protected from asbestos-induced pulmonary fibrosis, as determined by histological and biochemical analysis and suggests that a simple intervention may be useful to prevent progression of the disease.

Mitochondrial Rac1 GTPase Import and Electron Transfer from Cytochrome c Are Required for Pulmonary Fibrosis*

TLDR
This study shows that Rac1 is localized in the mitochondria of alveolar macrophages from asbestosis patients, and mitochondrial import requires the C-terminal cysteine of Rac1 (Cys-189), which is post-translationally modified by geranylgeranylation.

Oxidative stress, extracellular matrix targets, and idiopathic pulmonary fibrosis.

Inhibition of mechanosensitive signaling in myofibroblasts ameliorates experimental pulmonary fibrosis.

TLDR
It is indicated that targeting mechanosensitive signaling in myofibroblasts to trigger the intrinsic apoptosis pathway may be an effective approach for treatment of fibrotic disorders.

Accelerated Development of Pulmonary Fibrosis via Cu,Zn-superoxide Dismutase-induced Alternative Activation of Macrophages*

TLDR
It is demonstrated that Cu,Zn-SOD polarized macrophages to an M2 phenotype, and Cu,SOD-mediated H2O2 levels modulated M2 gene expression at the transcriptional level by redox regulation of a critical cysteine in STAT6.

Mitochondrial Cu,Zn-Superoxide Dismutase Mediates Pulmonary Fibrosis by Augmenting H2O2 Generation*

TLDR
A novel mechanism for the pathogenesis of pulmonary fibrosis where the antioxidant enzyme Cu,Zn-SOD translocates to the mitochondrial IMS to increase H2O2 generation in alveolar macrophages is demonstrated.

Mitochondrial Reactive Oxygen Species Regulate Transforming Growth Factor-β Signaling

TLDR
It is reported that mitochondrial reactive oxygen species (ROS) generated at complex III are required for TGF-β-induced gene expression in primary normal human lung fibroblasts and that targeting mitochondrial ROS might be beneficial in diseases associated with excessive fibrosis.

Modulation of the Mevalonate Pathway by Akt Regulates Macrophage Survival and Development of Pulmonary Fibrosis*

TLDR
It is found that Akt modulated the mevalonate pathway, which is also linked to cell survival, by increasing Rho GTPase activation, and this relationship enhanced macrophage survival in patients with pulmonary fibrosis and mice with a fibrotic phenotype.

Mitochondrial Complex III-generated Oxidants Activate ASK1 and JNK to Induce Alveolar Epithelial Cell Death following Exposure to Particulate Matter Air Pollution*

TLDR
It is concluded that particulate matter air pollution induces the generation of ROS primarily from site III of the mitochondrial electron transport chain and that these ROS activate the intrinsic apoptotic pathway through ASK1, JNK, and p53.

Statins and pulmonary fibrosis: the potential role of NLRP3 inflammasome activation.

TLDR
Statin use is associated with ILA among smokers in the COPDGene study and enhances bleomycin-induced lung inflammation and fibrosis in the mouse through a mechanism involving enhanced NLRP3-inflammasome activation, suggesting that statins may influence the susceptibility to, or progression of, ILD.
...