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This version published online on August 16, 2007
Endocrinology, doi:10.1210/en.2007-0765
A more recent version of this article appeared on November 1, 2007
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Submitted on June 11, 2007
Accepted on August 2, 2007

Kidney gene expression analysis in a rat model of intra uterine growth restriction reveals massive alterations of coagulation genes

Christophe Buffat, Farid Boubred, Françoise Mondon, Sonia T. Chelbi, Jean-Marc Feuerstein, Martine Lelièvre-Pégorier, Daniel Vaiman*, and Umberto Simeoni

Laboratoire de Biochimie et de Biologie Moléculaire, Hôpital La Conception, AP-HM, Marseille, France / Upres EA 2193 Faculté de Médecine, Marseille, France; Service de Médecine Néonatale, Hôpital de La Conception, AP-HM, Marseille, France /INSERM UMR608, Université de la Méditerranée, Marseille, France; Département de Génétique et Développement, Institut Cochin, Institut National de la Santé et de la Recherche Médicale U567, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, and Faculté de Médecine René Descartes, Université Paris V UM 3, 75014 Paris, France; CFREMC Centre de Formation et de Recherche Expérimental Medico-Chirurgicale, Faculté de Médecine Marseille, France ; INSERM U652, IFR 58, Centre de recherche des Cordeliers, Université René Descartes (Paris 5), Paris, France INRA Department of Animal Genetics, Jouy-en Josas, France

* To whom correspondence should be addressed. E-mail: vaiman{at}cochin.inserm.fr.

In this study, low birth weight was induced in rats by feeding the dams with a low protein diet during pregnancy. Kidneys from the foetuses at the end of gestation were collected and showed a reduction in overall and relative weight, in parallel with other tissues (heart and liver). This reduction was associated to a reduction in glomeruli number. To better understand the molecular basis of this observation, a transcriptome analysis contrasting kidneys from control and protein-deprived rats was performed, using a platform based upon long isothermic oligonucleotides, strengthening the robustness of the results. We could identify over 1,800 transcripts modified more than twice (772 induced and 1,040 repressed). Genes of either category were automatically classified according to functional criteria, making it possible to bring to light a large cluster of genes involved in coagulation and complement cascades. The promoters of the most induced and most repressed genes were contrasted for their composition in putative transcription factor binding sites, suggesting an overrepresentation of the AP1R binding site, together with the transcription induction of factors actually binding to this site in the set of induced genes.

The induction of coagulation cascades in the kidney of low birth weight rats provides a putative rationale for explaining thrombo-endothelial disorders also observed in intra-uterine growth-restricted human newborns. These alterations in the kidneys have been reported as a probable cause for cardiovascular diseases in the adult.







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