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1.
J Cell Biol ; 182(3): 459-65, 2008 Aug 11.
Article in English | MEDLINE | ID: mdl-18678710

ABSTRACT

Fibroblast growth factor 23 (FGF-23) and Klotho are secretory proteins that regulate mineral-ion metabolism. Fgf-23(-/-) or Klotho(-/-) knockout mice exhibit several pathophysiological processes consistent with premature aging including severe atrophy of tissues. We show that the signal transduction pathways initiated by FGF-23-Klotho prevent tissue atrophy by stimulating proliferation and preventing apoptosis caused by excessive systemic vitamin D. Because serum levels of active vitamin D are greatly increased upon genetic ablation of Fgf-23 or Klotho, we find that these molecules have a dual role in suppression of apoptotic actions of vitamin D through both negative regulation of 1alpha-hydroxylase expression and phosphoinositide-3 kinase-dependent inhibition of caspase activity. These data provide new insights into the physiological roles of FGF-23 and Klotho.


Subject(s)
Apoptosis/drug effects , Fibroblast Growth Factors/metabolism , Glucuronidase/metabolism , Vitamin D/pharmacology , Animals , Atrophy , Cell Line , Cell Proliferation/drug effects , Fibroblast Growth Factor-23 , Humans , Klotho Proteins , Mice , Signal Transduction/drug effects
2.
Nat Biotechnol ; 24(7): 832-40, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16823376

ABSTRACT

Over the last decade, gene expression microarrays have had a profound impact on biomedical research. The diversity of platforms and analytical methods available to researchers have made the comparison of data from multiple platforms challenging. In this study, we describe a framework for comparisons across platforms and laboratories. We have attempted to include nearly all the available commercial and 'in-house' platforms. Using probe sequences matched at the exon level improved consistency of measurements across the different microarray platforms compared to annotation-based matches. Generally, consistency was good for highly expressed genes, and variable for genes with lower expression values as confirmed by quantitative real-time (QRT)-PCR. Concordance of measurements was higher between laboratories on the same platform than across platforms. We demonstrate that, after stringent preprocessing, commercial arrays were more consistent than in-house arrays, and by most measures, one-dye platforms were more consistent than two-dye platforms.


Subject(s)
Chromosome Mapping/methods , Gene Expression Profiling/methods , Microarray Analysis/methods , Oligonucleotide Array Sequence Analysis/methods , DNA Probes/chemistry , DNA Probes/classification , Microarray Analysis/classification , Reproducibility of Results
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