Dwarfism Research Today is a free monthly online journal that collates and summarizes the latest research about Dwarfism, including details on genetics, diet, mental and motor development.

Genomic dissection of the cytokine controlled STAT5 signaling network in liver.

Hosui A, Hennighausen L

LGP, NIH, Bethesda, Maryland, United States.

Growth hormone controls the physiology and pathophysiology of the liver and its signals are conducted by two members of the family of Signal Transducers and Activators of Transcription, STAT5A and STAT5B. Mice from which the Stat5a/b locus has been inactivated specifically in hepatocytes display dwarfism, the expression of genes associated with liver metabolism and the cytochrome P450 system is greatly reduced and they develop hepatosteatosis. Several groups have shown by global gene expression profiling that a cadre of STAT5A/B target genes identify genetic cascades induced by growth hormone and other cytokines. Evidence is accumulating that in the absence of STAT5A/B growth hormone aberrantly activates STAT1 and STAT3 and their downstream target genes and thereby offers partial explanation of some of the physiological alterations observed in Stat5a/b-null mice and human patients. We hypothesize that phenotypic changes observed in the absence of STAT5A/B are due to two distinct molecular consequences. First, the failure of STAT5A/B target genes to be activated by growth hormone and secondly, the rerouting of growth hormone signaling to other members of the STAT family. Rerouting of GH signaling to STAT1 and STAT3 might partially compensate for the loss of STAT5A/B but it certainly activates biological programs distinct from STAT5A/B. Here we discuss to what extent studies on global gene expression profiling have fostered a better understanding of the biology behind cytokine-STAT5A/B networks in hepatocytes. We also explore whether this wealth of information on gene activity can be used to further understand the roles of cytokines in liver disease. Key words: STAT5, cytokines, liver, knock-out, metabolism.

Published 7 May 2008 in Physiol Genomics.
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Articles on Dwarfism published 2 May 2008:

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