A role for platelet-derived growth factor beta-receptor in a newborn rat model of endothelin-mediated pulmonary vascular remodeling
| Autor: | Rosetta Belcastro, Robert P. Jankov, A. Keith Tanswell, Soojin Yi, Crystal Kantores, Ross A. Ridsdale, Martin Post |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Pulmonary and Respiratory Medicine
Endothelin Receptor Antagonists medicine.medical_specialty Platelet-derived growth factor Vascular smooth muscle Receptor Platelet-Derived Growth Factor alpha Physiology medicine.medical_treatment Hypertension Pulmonary Becaplermin Carboxylic Acids Biology Pulmonary Artery Ligands Muscle Smooth Vascular Rats Sprague-Dawley Receptor Platelet-Derived Growth Factor beta chemistry.chemical_compound Pregnancy Physiology (medical) Internal medicine medicine Animals Receptor Cell Proliferation Platelet-Derived Growth Factor Lung Hyperplasia Endothelin-1 Cell growth Receptors Endothelin Growth factor Cell Biology Proto-Oncogene Proteins c-sis medicine.disease Pulmonary hypertension Rats Up-Regulation Oxygen Endocrinology medicine.anatomical_structure chemistry Animals Newborn Indans Models Animal Female Endothelin receptor |
| Zdroj: | American journal of physiology. Lung cellular and molecular physiology. 288(6) |
| ISSN: | 1040-0605 |
| Popis: | Newborn rats exposed to 60% O2for 14 days develop endothelin (ET)-1-dependent pulmonary hypertension with vascular remodeling, characterized by increased smooth muscle cell (SMC) proliferation and medial thickening of pulmonary resistance arteries. Using immunohistochemistry and Western blot analyses, we examined the effect of exposure to 60% O2on expression in the lung of receptors for the platelet-derived growth factors (PDGF), which are implicated in the pathogenesis of arterial smooth muscle hyperplasia. We observed a marked O2-induced upregulation of PDGF-α and -β receptors (PDGF-αR and -βR) on arterial smooth muscle. This led us to examine pulmonary vascular PDGF receptor expression in 60% O2-exposed rats given SB-217242, a combined ET receptor antagonist, which we found prevented the O2-induced upregulation of PDGF-βR, but not PDGF-αR, on arterial smooth muscle. PDGF-BB, a major PDGF-βR ligand, was found to be a potent in vitro inducer of hyperplasia and DNA synthesis in cultured pulmonary artery SMC from infant rats. A critical role for PDGF-βR ligands in arterial SMC proliferation was confirmed in vivo using a truncated soluble PDGF-βR intervention, which attenuated SMC proliferation induced by exposure to 60% O2. Collectively, these data are consistent with a major role for PDGF-βR-mediated SMC proliferation, acting downstream of increased ET-1 in a newborn rat model of 60% O2-induced pulmonary hypertension. |
| Databáze: | OpenAIRE |
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