Its major physiological targets are the epithelial cells, of which the most important are located in the distal nephron. Increasing our knowledge of adrenal physiology and gene regulation in nontransformed cell systems could lead us to a better approach for the discovery of candidate genes involved in pathological conditions of the adrenal cortex.Īldosterone controls sodium and potassium balance and also influences acid-base homeostasis in vertebrates ( 42, 60, 61).

This paper provides for the first time a complete study of the genes that are regulated, and the interaction between them, by aldosterone secretagogues in rat adrenal cells. Finally, data mining with gene promoters, transcription factors, and literature databases was performed to generate gene interaction networks for either ANG II or potassium. Differentially expressed genes were grouped according to their time response expression pattern, and their promoter regions were analyzed for common regulatory transcription factor binding sites. A subset of the most regulated genes was confirmed by real-time RT-PCR, and then their expression was analyzed in time curve studies. Genes belonging to the nucleic acid binding and transcription factor activity categories were significantly enriched. Several genes were differentially expressed by ANG II ( n = 133) or potassium ( n = 216). Freshly isolated rat adrenal zona glomerulosa cells were stimulated with the two main aldosterone secretagogues, angiotensin II and potassium, for 2 h and subjected to whole genome expression studies using multiple biological and bioinformatics tools.

The aim of this study was to determine the gene regulatory network triggered by aldosterone secretagogues in a nontransformed cell system.

Customer Service and Ordering Informationįrom the Institut National de la Santé et de la Recherche Médicale (S.B., B.S.-C., L.A., P.-F.P., X.J., T.M., M.-C.Z.), U970, Paris Cardiovascular Research Center, Paris, France University Paris Descartes (S.B., B.S.-C., L.A., P.-F.P., X.J., T.M., M.-C.Z.), Paris, France Institut des Hautes Études Scientifiques (J.-F.G.D., A.B.), Bures sur Yvette, France Institut National de la Santé et de la Recherche Médicale (H.L., E.Lo.), U982, Mont-Saint-Aignan, France University of Rouen (H.L., E.Lo.), Mont-Saint-Aignan, France University Hospital of Rouen (H.L.), Rouen, France Assistance Publique-Hôpitaux de Paris (L.A., P.-F.P., X.J., T.M., M.-C.Z.), Hôpital Européen Georges Pompidou, Paris, France Institut de Pharmacologie Moléculaire et Cellulaire (E.La.), Centre National de la Recherche Scientifique, Unité mixte de recherche 6097, Valbonne, France University Nice-Sophia Antipolis (E.La.), Nice, France Institut de Recherche Interdisciplinaire (A.B.), Centre National de la Recherche Scientifique, USR3078, University of Lille I and Lille II, Villeneuve d’Ascq, France.įrom the Institut National de la Santé et de la Recherche Médicale (S.B., B.S.-C., L.A., P.-F.P., X.J., T.M., M.-C.Z.), U970, Paris Cardiovascular Research Center, Paris, France University Paris Descartes (S.B., B.S.-C., L.A., P.-F.P., X.J., T.M., M.-C.Z.), Paris, France Institut des Hautes Études Scientifiques (J.-F.G.D., A.B.), Bures sur Yvette, France Institut National de la Santé et de la Recherche Médicale (H.L., E.Lo.), U982, Mont-Saint-Aignan, France University of Rouen (H.L., E.Lo.), Mont-Saint-Aignan, France University Hospital of Rouen (H.L.), Rouen, France Assistance Publique-Hôpitaux de Paris (L.A., P.-F.P., X.J., T.M., M.-C.Z.), Hôpital Européen Georges Pompidou, Paris, France Institut de Pharmacologie Moléculaire et Cellulaire (E.La.The mineralocorticoid aldosterone, mainly produced by the adrenal gland, is essential for life, but an abnormally excessive secretion causes severe pathological effects including hypertension and target organ injury in the heart and kidney.

Stroke: Vascular and Interventional Neurology.

Journal of the American Heart Association (JAHA).

Circ: Cardiovascular Quality & Outcomes.

Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB).

Zona glomerulosa