Inhibition of platelet-derived growth factor signaling attenuates pulmonary fibrosis

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