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. 2008 Jun;27(5):462-74.
doi: 10.1016/j.matbio.2008.01.009. Epub 2008 Apr 18.

Genetic networks of cooperative redox regulation of osteopontin

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Genetic networks of cooperative redox regulation of osteopontin

C R Partridge et al. Matrix Biol. 2008 Jun.

Abstract

Osteopontin is a primary cytokine and matrix-associated protein involved in medial thickening and neointima formation VSports手机版. 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 beta 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 beta inducible early gene 1 cis-acting elements in the regulation of osteopontin. .

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