Related Experiment Video

Updated: Aug 19, 2026

Oropharyngeal Administration of Bleomycin in the Murine Model of Pulmonary Fibrosis
06:03

Oropharyngeal Administration of Bleomycin in the Murine Model of Pulmonary Fibrosis

Published on: May 9, 2025

Inhibition of platelet-derived growth factor signaling attenuates pulmonary fibrosis

Amir Abdollahi1, Minglun Li, Gong Ping

  • 1Department of Radiation Oncology, German Cancer Research Center, Heidelberg 69120, Germany.

The Journal of Experimental Medicine
|March 23, 2005
PubMed

Insights

Platelet-derived growth factor receptor tyrosine kinase inhibitors (RTKIs) show promise in treating radiation-induced pulmonary fibrosis. These inhibitors attenuated lung fibrosis and improved survival in mice, suggesting a new therapeutic avenue.

Area of Science:

  • Oncology
  • Pulmonology
  • Pharmacology

Background:

  • Pulmonary fibrosis is a severe condition with limited treatment options.
  • Therapy-induced fibrosis can reduce the effectiveness of cancer treatments like chemotherapy and radiotherapy.
  • Platelet-derived growth factor (PDGF) signaling is implicated in fibrotic diseases.

Purpose of the Study:

  • To investigate the potential of PDGF receptor tyrosine kinase inhibitors (RTKIs) in mitigating radiation-induced pulmonary fibrosis.
  • To explore the role of PDGF signaling in the development of lung fibrosis following radiation exposure.

Main Methods:

  • C57BL/6 mice underwent thoracic irradiation (20 Gy).
  • Mice were treated with one of three PDGF RTKIs: SU9518, SU11657, or Imatinib.
  • Fibrosis development was assessed using clinical, histological, and computed tomography (CT) imaging; survival rates were monitored.

Main Results:

  • Irradiation induced significant pulmonary fibrosis and reduced mouse survival.
  • PDGF RTKI treatment markedly attenuated fibrosis development, correlating with clinical, histological, and CT findings.
  • RTKI treatment significantly prolonged the lifespan of irradiated mice.
  • Radiation increased PDGF (A-D) isoform expression and PDGF receptor phosphorylation, which was effectively inhibited by RTKIs.

Conclusions:

  • PDGF signaling plays a critical role in the pathogenesis of radiation-induced pulmonary fibrosis.
  • Inhibiting fibrogenesis, not just inflammation, is crucial for effective antifibrotic therapy.
  • PDGF RTKIs represent a potential therapeutic strategy for idiopathic and therapy-related lung fibrosis.

Related Concept Videos

Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists01:23

Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists

Prostacyclin receptor agonists are a class of therapeutic agents integral to managing pulmonary arterial hypertension (PAH). These drugs operate by mimicking the action of prostaglandin I2, or PGI2, a naturally occurring compound in the body.
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...
Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers01:26

Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers

Receptor tyrosine kinase inhibitors (TKIs) and calcium channel blockers (CCBs) are two critical categories of drugs employed in the treatment of pulmonary artery hypertension (PAH). PAH is a disease that causes high blood pressure in the pulmonary arteries, resulting in chest pain, fatigue, and shortness of breath.
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...