scholarly journals Dissecting the Dualistic Effects of Transforming Growth Factor (TGF)-β on Fibroproliferation and Extracellular Matrix Production in Primary Human Lung Fibroblasts - The Role of p38δ MAP Kinase

2009 ◽  
Vol 2 (1) ◽  
pp. 28-37 ◽  
Author(s):  
Katrin E. Hostettler ◽  
Stephanie Goulet ◽  
Michael Roth ◽  
Jun Zhong ◽  
Janette K. Burgess ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Map Kinase ◽  
Transforming Growth Factor ◽  
Human Lung ◽  
Lung Fibroblasts ◽  
Human Lung Fibroblasts ◽  
Extracellular Matrix Production ◽  
Matrix Production

scholarly journals Amplified canonical transforming growth factor-β signalling via heat shock protein 90 in pulmonary fibrosis

2016 ◽  
Vol 49 (2) ◽  
pp. 1501941 ◽  
Author(s):  
Zaneta Sibinska ◽  
Xia Tian ◽  
Martina Korfei ◽  
Baktybek Kojonazarov ◽  
Janina Susanne Kolb ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Pulmonary Fibrosis ◽  
Transforming Growth Factor ◽  
A549 Cells ◽  
Lung Fibroblasts ◽  
Hsp90 Inhibition ◽  
Extracellular Matrix Production ◽  
Matrix Production ◽  
Β Receptor

Interstitial lung fibroblast activation coupled with extracellular matrix production is a pathological signature of idiopathic pulmonary fibrosis (IPF), and is governed by transforming growth factor (TGF)-β/Smad signalling. We sought to define the role of heat shock protein (HSP)90 in profibrotic responses in IPF and to determine the therapeutic effects of HSP90 inhibition in a murine model of pulmonary fibrosis.We investigated the effects of HSP90 inhibition in vitro by applying 17-AAG (17-allylamino-17-demethoxygeldanamycin) to lung fibroblasts and A549 cells and in vivo by administering 17-DMAG (17-dimethylaminoethylamino-17-demethoxygeldanamycin) to mice with bleomycin-induced pulmonary fibrosis.HSP90 expression was increased in (myo)fibroblasts from fibrotic human and mouse lungs compared with controls. 17-AAG inhibited TGF-β1-induced extracellular matrix production and transdifferentiation of lung fibroblasts and epithelial–mesenchymal transition of A549 cells. The antifibrotic effects were associated with TGF-β receptor disruption and inhibition of Smad2/3 activation. Co-immunoprecipitation revealed that HSP90β interacted with TGF-β receptor II and stabilised TGF-β receptors. Furthermore, 17-DMAG improved lung function and decreased fibrosis and matrix metalloproteinase activity in the lungs of bleomycin-challenged mice.In conclusion, this is the first study to demonstrate that HSP90 inhibition blocks pulmonary fibroblast activation and ameliorates bleomycin-induced pulmonary fibrosis in mice.

Hypoxia modulates the effects of transforming growth factor-β isoforms on matrix-formation by primary human lung fibroblasts

Cytokine ◽  
2003 ◽  
Vol 24 (1-2) ◽  
pp. 25-35 ◽  
Author(s):  
Eleni Papakonstantinou ◽  
Alexios J Aletras ◽  
Michael Roth ◽  
Michael Tamm ◽  
George Karakiulakis
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Human Lung ◽  
Transforming Growth Factor Β ◽  
Lung Fibroblasts ◽  
Human Lung Fibroblasts
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