TAK1 inhibition attenuates both inflammation and fibrosis in experimental pneumoconiosis

@article{Li2017TAK1IA,
  title={TAK1 inhibition attenuates both inflammation and fibrosis in experimental pneumoconiosis},
  author={Jie Li and Chao Liang and Zong-Kang Zhang and Xiao-hua Pan and Songlin Peng and Wing-Sze Lee and Aiping Lu and Zhixiu Lin and Ge Zhang and Wing Nang Leung and Bao-Ting Zhang},
  journal={Cell Discovery},
  year={2017},
  volume={3}
}
Pneumoconiosis, caused by inhalation of mineral dusts, is a major occupational disease worldwide. Currently, there are no effective drugs owing to a lack of potential therapeutic targets during either the inflammation or fibrosis molecular events in pneumoconiosis. Here, we performed microarrays to identify aberrantly expressed genes in the above molecular events in vitro and found a hub gene transforming growth factor-β-activated kinase 1 (TAK1), which was highly expressed and activated in… 

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References

SHOWING 1-10 OF 72 REFERENCES

Silica-induced NLRP3 inflammasome activation in vitro and in rat lungs

DQ12 quartz exposure induced acute and chronic functional activation of the inflammasome in the heterogeneous cell populations of the lung in associated with its crystalline surface reactivity, indicating that the development of silicosis and inflammaome activation is determined by crystalline silica surface reactsivity.

New developments in the understanding of immunology in silicosis

  • F. Huaux
  • Medicine, Biology
    Current opinion in allergy and clinical immunology
  • 2007
New pathogenic routes involving innate receptors and antiinflammation as well as new antifibrotic immune mediators have been recently described in experimental silicosis, highlighting new potential therapeutic targets and strategies.

TAK1 inhibition prevents the development of autoimmune diabetes in NOD mice

The results indicate that TAK1 inhibition with OZ was associated with a lower frequency of autoimmune diabetes in NOD mice, and the net effect of Tak1 inhibition in Nod mice appears to be protective rather than disease-enhancing.

TAK1 Is a Central Mediator of NOD2 Signaling in Epidermal Cells*

It is shown that transforming growth factor β-activated kinase 1 (TAK1) is an essential intermediate of NOD2 signaling and its ablation may impair the skin barrier function leading to inflammation.

Silicosis: a review.

Amelioration of emphysema in mice through lentiviral transduction of long-lived pulmonary alveolar macrophages.

An intratracheally instilled lentiviral system able to deliver genes selectively to as many as 70% of alveolar macrophages (AMs) in the mouse lung is described and it is suggested that these differentiated cells may be a possible target cell population for in vivo gene therapy applications, including the sustained correction of hAAT deficiency.

Silicosis and coal workers' pneumoconiosis.

Exposure to coal mine dust and/or crystalline silica results in pneumoconiosis with initiation and progression of pulmonary fibrosis. This review presents characteristics of simple and complicated

The impact of TGF-β on lung fibrosis: from targeting to biomarkers.

This review will focus on discussing novel data and highlighting growing interest in deepening the understanding of the profibrotic role of TGF-β and its direct or indirect targeting for disease modulation.

Sirt1 Activation Ameliorates Renal Fibrosis by Inhibiting the TGF‐β/Smad3 Pathway

The results identify Sirt1 as an important protective factor for renal fibrosis in a CKD rodent model, and the protective function of Sirt 1 is attributable to its action on TGF‐β/Smad3 signaling.

Mechanistically Identified Suitable Biomarkers of Exposure, Effect, and Susceptibility for Silicosis and Coal-Worker'S Pneumoconiosis: A Comprehensive Review

A number of “ideal” biological markers of effect were identified, namely, Clara cell protein-16 (CC16) (serum), tumor necrosis factor-α (TNF-α) (Monocyte release), interleukin-8 (IL-8) (monocyte release) and reactive oxygen species (ROS) measurement by chemiluminescence (neutrophil release).
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