scholarly journals Inhibition of platelet-derived growth factor signaling attenuates pulmonary fibrosis

2005 ◽  
Vol 201 (6) ◽  
pp. 925-935 ◽  
Author(s):  
Amir Abdollahi ◽  
Minglun Li ◽  
Gong Ping ◽  
Christian Plathow ◽  
Sophie Domhan ◽  
...  

Pulmonary fibrosis is the consequence of a variety of diseases with no satisfying treatment option. Therapy-induced fibrosis also limits the efficacy of chemotherapy and radiotherapy in numerous cancers. Here, we studied the potential of platelet-derived growth factor (PDGF) receptor tyrosine kinase inhibitors (RTKIs) to attenuate radiation-induced pulmonary fibrosis. Thoraces of C57BL/6 mice were irradiated (20 Gy), and mice were treated with three distinct PDGF RTKIs (SU9518, SU11657, or Imatinib). Irradiation was found to induce severe lung fibrosis resulting in dramatically reduced mouse survival. Treatment with PDGF RTKIs markedly attenuated the development of pulmonary fibrosis in excellent correlation with clinical, histological, and computed tomography results. Importantly, RTKIs also prolonged the life span of irradiated mice. We found that radiation up-regulated expression of PDGF (A–D) isoforms leading to phosphorylation of PDGF receptor, which was strongly inhibited by RTKIs. Our findings suggest a pivotal role of PDGF signaling in the pathogenesis of pulmonary fibrosis and indicate that inhibition of fibrogenesis, rather than inflammation, is critical to antifibrotic treatment. This study points the way to a potential new approach for treating idiopathic or therapy-related forms of lung fibrosis.

1995 ◽  
Vol 270 (46) ◽  
pp. 27595-27600 ◽  
Author(s):  
Daruka Mahadevan ◽  
Jin-Chen Yu ◽  
Jose W. Saldanha ◽  
Narmada Thanki ◽  
Peter McPhie ◽  
...  

2006 ◽  
Vol 48 (11) ◽  
pp. 2315-2323 ◽  
Author(s):  
Pawel Zymek ◽  
Marcin Bujak ◽  
Khaled Chatila ◽  
Anna Cieslak ◽  
Geeta Thakker ◽  
...  

1991 ◽  
Vol 266 (30) ◽  
pp. 20232-20237 ◽  
Author(s):  
M.A. Heidaran ◽  
J.H. Pierce ◽  
J.C. Yu ◽  
D. Lombardi ◽  
J.E. Artrip ◽  
...  

1991 ◽  
Vol 5 (6) ◽  
pp. 503-504 ◽  
Author(s):  
William A. Marinelli ◽  
Vitaly A. Polunovsky ◽  
Keith R. Harmon ◽  
Peter B. Bitterman

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