Alveolar epithelial cell mesenchymal transition develops
            <i>in vivo</i>
            during pulmonary fibrosis and is regulated by the extracellular matrix

Kim, Kevin K.; Kugler, Matthias C.; Wolters, Paul J.; Robillard, Liliane; Galvez, Michael G.; Brumwell, Alexis; Sheppard, Dean; Chapman, Harold A.

doi:10.1073/pnas.0605669103

Cited by 1,158 publications

(1,169 citation statements)

References 27 publications

Supporting

Mentioning

1,105

Contrasting

Unclassified

Order By: Relevance

“…It is involved in a variety of normal physiological as well as pathological processes such as cancer progression and renal fibrosis (16,17). Recent evidence suggests a potential role for EMT in the pathogenesis of pulmonary fibrosis (14,15,(41)(42)(43). MFT is a similar process and has been described as a major factor in the development of peritoneal fibrosis (18).…”

Section: Discussionmentioning

confidence: 99%

TGF-β1 Induces Progressive Pleural Scarring and Subpleural Fibrosis

Decologne

Kolb

Margetts

et al. 2007

The Journal of Immunology

117

119

View full text Add to dashboard Cite

Pleural fibrosis is a misunderstood disorder which can cause severe restrictive lung disease with high morbidity and even mortality. The condition can develop in response to a large variety of diseases and tissue injury, among them infectious disease, asbestos, drugs, and radiation therapy. There is no efficient treatment to reverse established pleural fibrosis. TGF-β1 is suspected, even if not proven, as a key cytokine in this process. In this study, we used adenoviral gene transfer of TGF-β1 to the pleural mesothelium in rats. We show that local and transient TGF-β1 overexpression induces homogenous, prolonged, and progressive pleural fibrosis without pleurodesis, associated with severe impairment of pulmonary function. We further demonstrate that pleural fibrosis can expand into the lung parenchyma from the visceral layer, but not into the muscle from the parietal layer. We provide evidence that matrix accumulation and fibrosis within the parenchyma evolved through a process involving “mesothelial-fibroblastoid transformation” and suggest that the pleural mesothelial cell may be an important player involved in the development of the subpleural distribution pattern known to be a hallmark of pulmonary fibrosis. This new model of pleural fibrosis will allow us to better understand the mechanisms of progressive fibrogenesis, and to explore novel antifibrotic therapies in the pleural cavity.

show abstract

Section: Discussionmentioning

confidence: 99%

TGF-β1 Induces Progressive Pleural Scarring and Subpleural Fibrosis

Decologne

Kolb

Margetts

et al. 2007

The Journal of Immunology

117

119

View full text Add to dashboard Cite

show abstract

“…35 To determine the effects of MMP-3 on EMT, lung epithelial cells were cultured in the presence of MMP-3 for up to 72 hours. By 24 hours, the lung epithelial cells treated with MMP-3 displayed a distinctive change in cell morphology, with loss of cell-to-cell contacts and with cell spreading, unlike the morphology of control cells ( Figure 7A).…”

Section: Mmp-3 Induces Emt In Lung Epithelial Cellsmentioning

confidence: 99%

Matrix Metalloproteinase 3 Is a Mediator of Pulmonary Fibrosis

Yamashita

Dolgonos

Zemans

et al. 2011

The American Journal of Pathology

193

138

View full text Add to dashboard Cite

show abstract

“…Type II alveolar epithelial cells have been shown to acquire a fibroblast‐like phenotype through EMT to promote the progression of pulmonary fibrosis 3, 4. These cells promote collagen deposition in the extracellular matrix.…”

Section: Introductionmentioning

confidence: 99%

A positive feedback loop promotes HIF‐1α stability through miR‐210‐mediated suppression of RUNX3 in paraquat‐induced EMT

Zhu

Meng

Xie

et al. 2017

J Cellular Molecular Medi

View full text Add to dashboard Cite

Irreversible pulmonary fibrosis induced by paraquat (PQ) poisoning is the major cause of death in patients with PQ poisoning. The epithelial–mesenchymal transition (EMT) is postulated to be one of the main mechanisms of pulmonary fibrosis. Here, we investigated the role of miR‐210 in PQ‐induced EMT and its relationship with hypoxia‐inducible factor‐1α (HIF‐1α). Western blotting, immunofluorescence, immunoprecipitation and other methods were used in this study. We found that miR‐210 expression was significantly increased after PQ poisoning, and it may be regulated by HIF‐1α. Overexpression of miR‐210 further increased the HIF‐1α protein level and promoted EMT. Moreover, miR‐210 knock‐down reduced the HIF‐1α protein level and decreased the degree of EMT. Runt‐related transcription factor‐3 (RUNX3), a direct target of miR‐210, was inhibited by miR‐210 in response to PQ poisoning. RUNX3 increased the hydroxylation ability of prolyl hydroxylase domain‐containing protein 2 (PHD2), a key enzyme that promotes HIF‐1α degradation. PHD2 immunoprecipitated with RUNX3 and its level changed similarly to that of RUNX3. The expression of the HIF‐1α protein was significantly reduced when RUNX3 was overexpressed. HIF‐1α protein levels were markedly increased when RUNX3 was silenced. Based on these results, a positive feedback loop may exist between miR‐210 and HIF‐1α. The mechanism may function through miR‐210‐mediated repression of RUNX3, which further decreases the hydroxylation activity of PHD2, enhances the stability of HIF‐1α, and promotes PQ‐induced EMT, aggravating the progression of pulmonary fibrosis. This study further elucidates the mechanism of PQ‐induced pulmonary fibrosis and may provide a new perspective for the future development of therapies.

show abstract

Alveolar epithelial cell mesenchymal transition develops in vivo during pulmonary fibrosis and is regulated by the extracellular matrix

Cited by 1,158 publications

References 27 publications

TGF-β1 Induces Progressive Pleural Scarring and Subpleural Fibrosis

TGF-β1 Induces Progressive Pleural Scarring and Subpleural Fibrosis

Matrix Metalloproteinase 3 Is a Mediator of Pulmonary Fibrosis

A positive feedback loop promotes HIF‐1α stability through miR‐210‐mediated suppression of RUNX3 in paraquat‐induced EMT

Contact Info

Product

Resources

About