Smad signaling in the rat model of monocrotaline pulmonary hypertension

Margaret F. Ramos, Michael W. Lamé, Henry J. Segall, Dennis W Wilson

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Mutations in the bone morphogenetic protein receptor type II (BMPrII) gene have been implicated in the development of familial pulmonary artery hypertension (PAH). The function of BMP signal transduction within the pulmonary vasculature and the role BMPrII mutations have in the development of PAH are incompletely understood. We used the monocrotaline (MCT) model of PAH to examine alterations in Smad signal transduction pathways in vivo. Lungs harvested from Sprague-Dawley rats treated with a single 60-mg/kg intraperitoneal (IP) injection of MCT were compared to saline-treated controls 2 weeks following treatment. Smad 4 was localized by immunohistochemistry to endothelial nuclei of the intra-acinar vessels undergoing remodeling. Smad 4, common to both BMP and transforming growth factor β (TGFβ) signaling, and BMP-specific Smad 1 were significantly decreased in western blot from whole lungs of treated animals, while no change was found for TGFβ-specific Smad 2. MCT-treated rats also had increased expression of phosphorylated Smad 1 (P-Smad 1) but not phosphorylated Smad 2 (P-Smad 2). There was a decrease in the expression of the full BMPrII protein but not its short form variant in MCT-treated rat lungs. The type I receptor Alk1 had increased expression. Collectively, our data indicate that vascular remodeling in the MCT model is associated with alterations in BMP receptors and persistent endothelial Smad 1 signaling.

Original languageEnglish (US)
Pages (from-to)311-320
Number of pages10
JournalToxicologic Pathology
Volume36
Issue number2
DOIs
StatePublished - Feb 2008

Keywords

  • BMP receptors
  • Monocrotaline
  • Pulmonary hypertension
  • Smad signal transduction

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Toxicology
  • Health, Toxicology and Mutagenesis

Fingerprint Dive into the research topics of 'Smad signaling in the rat model of monocrotaline pulmonary hypertension'. Together they form a unique fingerprint.

  • Cite this