Inhibition of hSP-B promoter in respiratory epithelial cells by a dominant negative retinoic acid receptor

Manely Ghaffari, Jeffrey A. Whitsett, Cong Yan

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Retinoic acid (RA) receptors (RARs) belong to the nuclear hormone receptor superfamily and play important roles in lung differentiation, growth, and gene regulation. Surfactant protein (SP) B is a small hydrophobic protein synthesized and secreted by respiratory epithelial cells in the lung. Expression of the SP-B gene is modulated at the transcriptional and posttranscriptional levels. In the present work, immunohistochemical staining revealed that RAR-α is present on day 14.5 of gestation in the fetal mouse lung. To assess whether RAR is required for SP-B gene transcription, a dominant negative mutant human (h) RAR-α403 was generated. The hRAR-α403 mutant was transcribed and translated into the truncated protein product by reticulocyte lysate in vitro. The mutant retained DNA binding activity in the presence of retinoid X receptor-γ to an RA response element in the hSP-B promoter. When transiently transfected into pulmonary adenocarcinoma epithelial cells (H441 cells), the mutant hRAR-α403 was readily detected in the cell nucleus. Cotransfection of the mutant hRAR-α403 repressed activity of the hSP-B promoter and inhibited RA-induced surfactant proprotein B production in H441 cells, supporting the concept that RAR is required for hSP-B gene transcription in vitro.

Original languageEnglish (US)
Pages (from-to)L398-L404
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume276
Issue number3 20-3
StatePublished - Mar 1 1999
Externally publishedYes

Keywords

  • Human surfactant protein B
  • Lung development
  • Nuclear receptors

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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