scholarly journals Integration of Transcriptomic and Proteomic Profiles Identifies Potential Biomarkers in Idiopathic Pulmonary Fibrosis

Author(s):  
Peiyan Zheng ◽  
Shixue Sun ◽  
Jingxian Wang ◽  
Zhangkai Jason Cheng ◽  
Kuan Cheok Lei ◽  
...  

Abstract Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by chronic progressive pulmonary fibrosis and a poor prognosis. Till now, no studies have been reported on revealing mechanisms and identifying biomarkers by integratively analyzing transcriptome and proteomes of IPF patients. Here we examined the landscape of IPF patients' gene expression in the transcription and translation phases and investigated the expression and functions of two new potential biomarkers. Differentially expressed (DE) mRNAs were mainly enriched in pathways of immune system activities and inflammatory responses, while DE proteins are associated with extracellular matrix production and wound repair. The upregulated genes in both phases are associated with wound repair and cell differentiation, while the downregulated genes in both phases are associated with reduced immune activities and the damage of the alveolar tissues. On this basis, we identified thirteen potential marker genes. Among them, we validated the expression changes of BTNL9 and PLLP and investigated their functional pathways in the IPF mechanism. Both genes are downregulated in the tissues of IPF patients and Bleomycin-induced mice, and co-expression analysis indicates that they have a protective effect by inhibiting extracellular matrix production and promoting wound repair in alveolar epithelial cells.

2016 ◽  
Vol 49 (2) ◽  
pp. 1501941 ◽  
Author(s):  
Zaneta Sibinska ◽  
Xia Tian ◽  
Martina Korfei ◽  
Baktybek Kojonazarov ◽  
Janina Susanne Kolb ◽  
...  

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.


Author(s):  
Ulrich A. Stock ◽  
Dmitri Wiederschain ◽  
Susan M. Kilroy ◽  
Dominique Shum-Tim ◽  
Philip N. Khalil ◽  
...  

2009 ◽  
Vol 337 (1) ◽  
pp. 103-111 ◽  
Author(s):  
Cheng-Juan Qu ◽  
Teemu Pöytäkangas ◽  
Marjo Jauhiainen ◽  
Seppo Auriola ◽  
Mikko J. Lammi

2007 ◽  
Vol 26 (2) ◽  
pp. 106-114 ◽  
Author(s):  
Robert F. Klees ◽  
Roman M. Salasznyk ◽  
Scott Vandenberg ◽  
Kristin Bennett ◽  
George E. Plopper

2010 ◽  
Vol 111 (3) ◽  
pp. 585-596 ◽  
Author(s):  
Christina K. Chan ◽  
Marsha W. Rolle ◽  
Susan Potter-Perigo ◽  
Kathleen R. Braun ◽  
Benjamin P. Van Biber ◽  
...  

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