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Research by C. Buffat and colleagues in RNA research provides new insights
November 19th, 2007
2007 NOV 19 -- Research findings, 'A hierarchical analysis of transcriptome alterations in intrauterine growth restriction (IUGR) reveals common pathophysiological pathways in mammals,' are discussed in a new report. "Intra-uterine growth restriction (IUGR) is a frequent disease, affecting up to 10% of human pregnancies and responsible for increased perinatal morbidity and mortality. Moreover, low birth weight is an important cause of the metabolic syndrome in the adult," scientists in Marseille, France report. "Protein depletion during the gestation of rat females has been widely used as a model for human IUGR. By transcriptome analysis of control and protein-deprived rat placentas, we were able to identify 2543 transcripts modified more than 2.5 fold (1347 induced and 1196 repressed). Automatic functional classification enabled us to identify clusters of induced genes affecting chromosome structure, transcription, intracellular transport, protein modifications and apoptosis. In particular, we suggest the existence of a complex balance regulating apoptosis. Among repressed genes, we noted several groups of genes involved in immunity, signalling and degradation of noxious chemicals. These observations suggest that IUGR placentas have a decreased resistance to external aggression. The promoters of the most induced and most repressed genes were contrasted for their composition in putative transcription factor binding sites. There was an over-representation of Zn finger (ZNF) proteins and Pdx1 (pancreatic and duodenal homeobox protein 1) putative binding sites. Consistently, Pdx1 and a high proportion of ZNF genes were induced at the transcriptional level. A similar analysis of ZNF promoters showed an increased presence of putative binding sites for the Tata box binding protein (Tbp). Consistently again, we showed that the Tbp and TBP-associated factors (Tafs) were up-regulated in IUGR placentas. Also, samples of human IUGR and control placentas showed that human orthologous ZNFs and PDX1 were transcriptionally induced, especially in non-vascular IUGR," wrote C. Buffat and colleagues, . The researchers concluded: "Immunohistochemistry revealed increased expression of PDX1 in IUGR human placentasour approach permitted the proposition of hypotheses on a hierarchy of gene inductions/repressions leading to massive transcriptional alterations in the IUGR placenta, in humans and in rodents." Buffat and colleagues published their study in the Journal of Pathology (A hierarchical analysis of transcriptome alterations in intrauterine growth restriction (IUGR) reveals common pathophysiological pathways in mammals. Journal of Pathology, 2007;213(3):337-46). For additional information, contact C. Buffat, Laboratoire de Biochimie et de Biologie Moleculaire, Hopital La Conception, AP-HM, Marseille, Upres EA 2193 Faculte de Medecine, Marseille, France. The publisher's contact information for the Journal of Pathology is: John Wiley & Sons Ltd., the Atrium, Southern Gate, Chichester PO19 8SQ, W Sussex, England. Keywords: France, Marseille, Apoptosis, Biotechnology, Cell Transport, Fetal Growth Retardation, Gene Therapy, Pathology, RNA Research, Therapy, Treatment. This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2007, Biotech Business Week via NewsRx.com.
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