title: Transcriptome Analysis of Human Reninomas as an Approach to Understanding Juxtaglomerular Cell Biology.
abstract: Renin, a key component in the regulation of blood pressure in mammals, is produced by the rare and highly specialized juxtaglomerular cells of the kidney. Chronic stimulation of renin release results in a recruitment of new juxtaglomerular cells by the apparent conversion of adjacent smooth muscle cells along the afferent arterioles. Because juxtaglomerular cells rapidly dedifferentiate when removed from the kidney, their developmental origin and the mechanism that explains their phenotypic plasticity remain unclear. To overcome this limitation, we have performed RNA expression analysis on 4 human renin-producing tumors. The most highly expressed genes that were common between the reninomas were subsequently used for in situ hybridization in kidneys of 5-day-old mice, adult mice, and adult mice treated with captopril. From the top 100 genes, 10 encoding for ligands were selected for further analysis. Medium of human embryonic kidney 293 cells transfected with the mouse cDNA encoding these ligands was applied to (pro)renin-synthesizing As4.1 cells. Among the ligands, only platelet-derived growth factor B reduced the medium and cellular (pro)renin levels, as well as As4.1 renin gene expression. In addition, platelet-derived growth factor B-exposed As4.1 cells displayed a more elongated and aligned shape with no alteration in viability. This was accompanied by a downregulated expression of α-smooth muscle actin and an upregulated expression of interleukin-6, suggesting a phenotypic shift from myoendocrine to inflammatory. Our results add 36 new genes to the list that characterize renin-producing cells and reveal a novel role for platelet-derived growth factor B as a regulator of renin-synthesizing cells.
authors.affiliation: From the Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands (A.G.M., E.C.H.F., A.H.v.d.M., A.H.J.D.); Laboratory of Molecular Biochemistry of Hypertension (L.K.X., M.-J.L., C.M., T.L.R.) and Laboratory of Bioinformatics and Computational Genomics (A.B.-C., B.H.-K.), Institut de Recherches Cliniques de Montréal (IRCM), Quebec, Canada; Division of Experimental Medicine, Faculty of Medicine, McGill University, Montréal, Quebec, Canada (L.K.X., T.L.R.); Department of Biochemistry (B.H.-K., T.L.R.) and Department of Medicine (T.L.R.), Université de Montréal, Quebec, Canada; Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY (K.W.G.); Hôpital Européen Georges Pompidou, Centre d'Investigations Cliniques 1418, Paris, France (M.A.); Collège de France, Center for Interdisciplinary Research in Biology (CIRB), Paris, France (P.C., G.N.); and INSERM, U1050, Paris, France (G.N.).
authors.forename: Alexandre G
authors.initials: AG
authors.lastname: Martini
authors.affiliation: From the Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands (A.G.M., E.C.H.F., A.H.v.d.M., A.H.J.D.); Laboratory of Molecular Biochemistry of Hypertension (L.K.X., M.-J.L., C.M., T.L.R.) and Laboratory of Bioinformatics and Computational Genomics (A.B.-C., B.H.-K.), Institut de Recherches Cliniques de Montréal (IRCM), Quebec, Canada; Division of Experimental Medicine, Faculty of Medicine, McGill University, Montréal, Quebec, Canada (L.K.X., T.L.R.); Department of Biochemistry (B.H.-K., T.L.R.) and Department of Medicine (T.L.R.), Université de Montréal, Quebec, Canada; Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY (K.W.G.); Hôpital Européen Georges Pompidou, Centre d'Investigations Cliniques 1418, Paris, France (M.A.); Collège de France, Center for Interdisciplinary Research in Biology (CIRB), Paris, France (P.C., G.N.); and INSERM, U1050, Paris, France (G.N.).
authors.forename: Lucie K
authors.initials: LK
authors.lastname: Xa
authors.affiliation: From the Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands (A.G.M., E.C.H.F., A.H.v.d.M., A.H.J.D.); Laboratory of Molecular Biochemistry of Hypertension (L.K.X., M.-J.L., C.M., T.L.R.) and Laboratory of Bioinformatics and Computational Genomics (A.B.-C., B.H.-K.), Institut de Recherches Cliniques de Montréal (IRCM), Quebec, Canada; Division of Experimental Medicine, Faculty of Medicine, McGill University, Montréal, Quebec, Canada (L.K.X., T.L.R.); Department of Biochemistry (B.H.-K., T.L.R.) and Department of Medicine (T.L.R.), Université de Montréal, Quebec, Canada; Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY (K.W.G.); Hôpital Européen Georges Pompidou, Centre d'Investigations Cliniques 1418, Paris, France (M.A.); Collège de France, Center for Interdisciplinary Research in Biology (CIRB), Paris, France (P.C., G.N.); and INSERM, U1050, Paris, France (G.N.).
authors.forename: Marie-Josée
authors.initials: MJ
authors.lastname: Lacombe
authors.affiliation: From the Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands (A.G.M., E.C.H.F., A.H.v.d.M., A.H.J.D.); Laboratory of Molecular Biochemistry of Hypertension (L.K.X., M.-J.L., C.M., T.L.R.) and Laboratory of Bioinformatics and Computational Genomics (A.B.-C., B.H.-K.), Institut de Recherches Cliniques de Montréal (IRCM), Quebec, Canada; Division of Experimental Medicine, Faculty of Medicine, McGill University, Montréal, Quebec, Canada (L.K.X., T.L.R.); Department of Biochemistry (B.H.-K., T.L.R.) and Department of Medicine (T.L.R.), Université de Montréal, Quebec, Canada; Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY (K.W.G.); Hôpital Européen Georges Pompidou, Centre d'Investigations Cliniques 1418, Paris, France (M.A.); Collège de France, Center for Interdisciplinary Research in Biology (CIRB), Paris, France (P.C., G.N.); and INSERM, U1050, Paris, France (G.N.).
authors.forename: Alexis
authors.initials: A
authors.lastname: Blanchet-Cohen
authors.affiliation: From the Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands (A.G.M., E.C.H.F., A.H.v.d.M., A.H.J.D.); Laboratory of Molecular Biochemistry of Hypertension (L.K.X., M.-J.L., C.M., T.L.R.) and Laboratory of Bioinformatics and Computational Genomics (A.B.-C., B.H.-K.), Institut de Recherches Cliniques de Montréal (IRCM), Quebec, Canada; Division of Experimental Medicine, Faculty of Medicine, McGill University, Montréal, Quebec, Canada (L.K.X., T.L.R.); Department of Biochemistry (B.H.-K., T.L.R.) and Department of Medicine (T.L.R.), Université de Montréal, Quebec, Canada; Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY (K.W.G.); Hôpital Européen Georges Pompidou, Centre d'Investigations Cliniques 1418, Paris, France (M.A.); Collège de France, Center for Interdisciplinary Research in Biology (CIRB), Paris, France (P.C., G.N.); and INSERM, U1050, Paris, France (G.N.).
authors.forename: Chantal
authors.initials: C
authors.lastname: Mercure
authors.affiliation: From the Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands (A.G.M., E.C.H.F., A.H.v.d.M., A.H.J.D.); Laboratory of Molecular Biochemistry of Hypertension (L.K.X., M.-J.L., C.M., T.L.R.) and Laboratory of Bioinformatics and Computational Genomics (A.B.-C., B.H.-K.), Institut de Recherches Cliniques de Montréal (IRCM), Quebec, Canada; Division of Experimental Medicine, Faculty of Medicine, McGill University, Montréal, Quebec, Canada (L.K.X., T.L.R.); Department of Biochemistry (B.H.-K., T.L.R.) and Department of Medicine (T.L.R.), Université de Montréal, Quebec, Canada; Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY (K.W.G.); Hôpital Européen Georges Pompidou, Centre d'Investigations Cliniques 1418, Paris, France (M.A.); Collège de France, Center for Interdisciplinary Research in Biology (CIRB), Paris, France (P.C., G.N.); and INSERM, U1050, Paris, France (G.N.).
authors.forename: Benjamin
authors.initials: B
authors.lastname: Haibe-Kains
authors.affiliation: From the Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands (A.G.M., E.C.H.F., A.H.v.d.M., A.H.J.D.); Laboratory of Molecular Biochemistry of Hypertension (L.K.X., M.-J.L., C.M., T.L.R.) and Laboratory of Bioinformatics and Computational Genomics (A.B.-C., B.H.-K.), Institut de Recherches Cliniques de Montréal (IRCM), Quebec, Canada; Division of Experimental Medicine, Faculty of Medicine, McGill University, Montréal, Quebec, Canada (L.K.X., T.L.R.); Department of Biochemistry (B.H.-K., T.L.R.) and Department of Medicine (T.L.R.), Université de Montréal, Quebec, Canada; Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY (K.W.G.); Hôpital Européen Georges Pompidou, Centre d'Investigations Cliniques 1418, Paris, France (M.A.); Collège de France, Center for Interdisciplinary Research in Biology (CIRB), Paris, France (P.C., G.N.); and INSERM, U1050, Paris, France (G.N.).
authors.forename: Edith C H
authors.initials: ECH
authors.lastname: Friesema
authors.affiliation: From the Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands (A.G.M., E.C.H.F., A.H.v.d.M., A.H.J.D.); Laboratory of Molecular Biochemistry of Hypertension (L.K.X., M.-J.L., C.M., T.L.R.) and Laboratory of Bioinformatics and Computational Genomics (A.B.-C., B.H.-K.), Institut de Recherches Cliniques de Montréal (IRCM), Quebec, Canada; Division of Experimental Medicine, Faculty of Medicine, McGill University, Montréal, Quebec, Canada (L.K.X., T.L.R.); Department of Biochemistry (B.H.-K., T.L.R.) and Department of Medicine (T.L.R.), Université de Montréal, Quebec, Canada; Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY (K.W.G.); Hôpital Européen Georges Pompidou, Centre d'Investigations Cliniques 1418, Paris, France (M.A.); Collège de France, Center for Interdisciplinary Research in Biology (CIRB), Paris, France (P.C., G.N.); and INSERM, U1050, Paris, France (G.N.).
authors.forename: Anton H
authors.initials: AH
authors.lastname: van den Meiracker
authors.affiliation: From the Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands (A.G.M., E.C.H.F., A.H.v.d.M., A.H.J.D.); Laboratory of Molecular Biochemistry of Hypertension (L.K.X., M.-J.L., C.M., T.L.R.) and Laboratory of Bioinformatics and Computational Genomics (A.B.-C., B.H.-K.), Institut de Recherches Cliniques de Montréal (IRCM), Quebec, Canada; Division of Experimental Medicine, Faculty of Medicine, McGill University, Montréal, Quebec, Canada (L.K.X., T.L.R.); Department of Biochemistry (B.H.-K., T.L.R.) and Department of Medicine (T.L.R.), Université de Montréal, Quebec, Canada; Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY (K.W.G.); Hôpital Européen Georges Pompidou, Centre d'Investigations Cliniques 1418, Paris, France (M.A.); Collège de France, Center for Interdisciplinary Research in Biology (CIRB), Paris, France (P.C., G.N.); and INSERM, U1050, Paris, France (G.N.).
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Gross
authors.affiliation: From the Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands (A.G.M., E.C.H.F., A.H.v.d.M., A.H.J.D.); Laboratory of Molecular Biochemistry of Hypertension (L.K.X., M.-J.L., C.M., T.L.R.) and Laboratory of Bioinformatics and Computational Genomics (A.B.-C., B.H.-K.), Institut de Recherches Cliniques de Montréal (IRCM), Quebec, Canada; Division of Experimental Medicine, Faculty of Medicine, McGill University, Montréal, Quebec, Canada (L.K.X., T.L.R.); Department of Biochemistry (B.H.-K., T.L.R.) and Department of Medicine (T.L.R.), Université de Montréal, Quebec, Canada; Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY (K.W.G.); Hôpital Européen Georges Pompidou, Centre d'Investigations Cliniques 1418, Paris, France (M.A.); Collège de France, Center for Interdisciplinary Research in Biology (CIRB), Paris, France (P.C., G.N.); and INSERM, U1050, Paris, France (G.N.).
authors.forename: Michel
authors.initials: M
authors.lastname: Azizi
authors.affiliation: From the Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands (A.G.M., E.C.H.F., A.H.v.d.M., A.H.J.D.); Laboratory of Molecular Biochemistry of Hypertension (L.K.X., M.-J.L., C.M., T.L.R.) and Laboratory of Bioinformatics and Computational Genomics (A.B.-C., B.H.-K.), Institut de Recherches Cliniques de Montréal (IRCM), Quebec, Canada; Division of Experimental Medicine, Faculty of Medicine, McGill University, Montréal, Quebec, Canada (L.K.X., T.L.R.); Department of Biochemistry (B.H.-K., T.L.R.) and Department of Medicine (T.L.R.), Université de Montréal, Quebec, Canada; Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY (K.W.G.); Hôpital Européen Georges Pompidou, Centre d'Investigations Cliniques 1418, Paris, France (M.A.); Collège de France, Center for Interdisciplinary Research in Biology (CIRB), Paris, France (P.C., G.N.); and INSERM, U1050, Paris, France (G.N.).
authors.forename: Pierre
authors.initials: P
authors.lastname: Corvol
authors.affiliation: From the Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands (A.G.M., E.C.H.F., A.H.v.d.M., A.H.J.D.); Laboratory of Molecular Biochemistry of Hypertension (L.K.X., M.-J.L., C.M., T.L.R.) and Laboratory of Bioinformatics and Computational Genomics (A.B.-C., B.H.-K.), Institut de Recherches Cliniques de Montréal (IRCM), Quebec, Canada; Division of Experimental Medicine, Faculty of Medicine, McGill University, Montréal, Quebec, Canada (L.K.X., T.L.R.); Department of Biochemistry (B.H.-K., T.L.R.) and Department of Medicine (T.L.R.), Université de Montréal, Quebec, Canada; Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY (K.W.G.); Hôpital Européen Georges Pompidou, Centre d'Investigations Cliniques 1418, Paris, France (M.A.); Collège de France, Center for Interdisciplinary Research in Biology (CIRB), Paris, France (P.C., G.N.); and INSERM, U1050, Paris, France (G.N.).
authors.forename: Geneviève
authors.initials: G
authors.lastname: Nguyen
authors.affiliation: From the Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands (A.G.M., E.C.H.F., A.H.v.d.M., A.H.J.D.); Laboratory of Molecular Biochemistry of Hypertension (L.K.X., M.-J.L., C.M., T.L.R.) and Laboratory of Bioinformatics and Computational Genomics (A.B.-C., B.H.-K.), Institut de Recherches Cliniques de Montréal (IRCM), Quebec, Canada; Division of Experimental Medicine, Faculty of Medicine, McGill University, Montréal, Quebec, Canada (L.K.X., T.L.R.); Department of Biochemistry (B.H.-K., T.L.R.) and Department of Medicine (T.L.R.), Université de Montréal, Quebec, Canada; Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY (K.W.G.); Hôpital Européen Georges Pompidou, Centre d'Investigations Cliniques 1418, Paris, France (M.A.); Collège de France, Center for Interdisciplinary Research in Biology (CIRB), Paris, France (P.C., G.N.); and INSERM, U1050, Paris, France (G.N.).
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Reudelhuber
authors.affiliation: From the Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands (A.G.M., E.C.H.F., A.H.v.d.M., A.H.J.D.); Laboratory of Molecular Biochemistry of Hypertension (L.K.X., M.-J.L., C.M., T.L.R.) and Laboratory of Bioinformatics and Computational Genomics (A.B.-C., B.H.-K.), Institut de Recherches Cliniques de Montréal (IRCM), Quebec, Canada; Division of Experimental Medicine, Faculty of Medicine, McGill University, Montréal, Quebec, Canada (L.K.X., T.L.R.); Department of Biochemistry (B.H.-K., T.L.R.) and Department of Medicine (T.L.R.), Université de Montréal, Quebec, Canada; Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY (K.W.G.); Hôpital Européen Georges Pompidou, Centre d'Investigations Cliniques 1418, Paris, France (M.A.); Collège de France, Center for Interdisciplinary Research in Biology (CIRB), Paris, France (P.C., G.N.); and INSERM, U1050, Paris, France (G.N.). a.danser@erasmusmc.nl.
authors.forename: A H Jan
authors.initials: AHJ
authors.lastname: Danser
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D017403:In Situ Hybridization; D007606:Juxtaglomerular Apparatus / Q000166:cytology* / Q000378:metabolism; D007674:Kidney Diseases / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011897:Random Allocation; D012083:Renin / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction
chemical_list: D010982:Platelet-Derived Growth Factor; D012083:Renin
keywords: gene expression; hypertension; platelet-derived growth factor; renin-producing tumor; transcriptome