Genetic networks of cooperative redox regulation of osteopontin

C. R. Partridge, Q. He, M. Brun, K. S. Ramos

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Osteopontin is a primary cytokine and matrix-associated protein involved in medial thickening and neointima formation. Osteopontin binds integrin receptors, activates cell migration and matrix metalloproteinases, and mediates arteriosclerotic lesion formation and vessel calcification. To understand the complex biology of osteopontin, computational methodology was employed to identify sets of genes whose transcriptional states were predictive of osteopontin gene expression based on the transcriptional states of 12,400 genes and ESTs across 235 independent Affymetrix Murine Genome Array MG_U74Av2 hybridizations. Arginase [GenBank: U51805] and Mac-2 antigen [GenBank: X16834] were identified as primary attractors within the gene-gene interaction network of osteopontin. Resolution of molecular interactions among these genes indicated that the majority of predictor genes could be linked through redox regulated transcription by nuclear factor kappa-B and transforming growth factor β inducible early gene 1 regulatory elements. Subsequent molecular analyses established redox sensitivity of a 200 bp region within the 5′ UTR of opn promoter and implicated nuclear factor kappa-B and transforming growth factor β inducible early gene 1 cis-acting elements in the regulation of osteopontin.

Original languageEnglish (US)
Pages (from-to)462-474
Number of pages13
JournalMatrix Biology
Volume27
Issue number5
DOIs
StatePublished - Jun 1 2008
Externally publishedYes

Keywords

  • Computational prediction
  • NF-kappa-B
  • Osteopontin
  • Oxidative stress
  • TGFβ1

ASJC Scopus subject areas

  • Molecular Biology

Fingerprint Dive into the research topics of 'Genetic networks of cooperative redox regulation of osteopontin'. Together they form a unique fingerprint.

  • Cite this