title: Prokineticin receptor 1 is required for mesenchymal-epithelial transition in kidney development.
abstract: Identification of factors regulating renal development is important to understand the pathogenesis of congenital kidney diseases. Little is known about the molecular mechanism of renal development and functions triggered by the angiogenic hormone prokineticin-2 and its receptor, PKR1. Utilizing the Gata5 (G5)-Cre and Wilms tumor 1 (Wt1)(GFP)cre transgenic lines, we generated mutant mice with targeted PKR1 gene disruptions in nephron progenitors. These mutant mice exhibited partial embryonic and postnatal lethality. Kidney developmental defects in PKR(G5-/-) mice are manifested in the adult stage as renal atrophy with glomerular defects, nephropathy, and uremia. PKR1(Wt1-/-) embryos exhibit hypoplastic kidneys with premature glomeruli and necrotic nephrons as a result of impaired proliferation and increased apoptosis in Wt1(+) renal mesenchymal cells. PKR1 regulates renal mesenchymal-epithelial transition (MET) that is involved in formation of renal progenitors, regulating glomerulogenesis toward forming nephrons during kidney development. In the isolated embryonic Wt1(+) renal cells, overexpression or activation of PKR1 promotes MET defined by the transition from elongated cell to octagonal cell morphology, and alteration of the expression of MET markers via activating NFATc3 signaling. Together, these results establish PKR1 via NFATc3 as a crucial modifier of MET processing to the development of nephron. Our study should facilitate new therapeutic opportunities in human renal disorders.-Arora, H., Boulberdaa, M., Qureshi, R., Bitirim, V., Messadeq, N., Dolle, P., Nebigil, C. G. Prokineticin receptor 1 is required for mesenchymal-epithelial transition in kidney development.
authors.affiliation: Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg, Unité Mixte de Recherche (UMR) 7242, Ecole Supérieure de Biotechnologie de Strasbourg, Illkirch, France; and.
authors.forename: Himanshu
authors.initials: H
authors.lastname: Arora
authors.affiliation: Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg, Unité Mixte de Recherche (UMR) 7242, Ecole Supérieure de Biotechnologie de Strasbourg, Illkirch, France; and.
authors.forename: Mounia
authors.initials: M
authors.lastname: Boulberdaa
authors.affiliation: Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg, Unité Mixte de Recherche (UMR) 7242, Ecole Supérieure de Biotechnologie de Strasbourg, Illkirch, France; and.
authors.forename: Rehana
authors.initials: R
authors.lastname: Qureshi
authors.affiliation: Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg, Unité Mixte de Recherche (UMR) 7242, Ecole Supérieure de Biotechnologie de Strasbourg, Illkirch, France; and.
authors.forename: Verda
authors.initials: V
authors.lastname: Bitirim
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, UMR 7104 and INSERM Unité 964, Université de Strasbourg, Illkirch-Strasbourg, France.
authors.forename: Nadia
authors.initials: N
authors.lastname: Messadeq
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, UMR 7104 and INSERM Unité 964, Université de Strasbourg, Illkirch-Strasbourg, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Dolle
authors.affiliation: Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg, Unité Mixte de Recherche (UMR) 7242, Ecole Supérieure de Biotechnologie de Strasbourg, Illkirch, France; and nebigil@unistra.fr.
authors.forename: Canan G
authors.initials: CG
authors.lastname: Nebigil
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D004622:Embryo, Mammalian / Q000378:metabolism; D047108:Embryonic Development; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D018919:Neovascularization, Physiologic; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*
chemical_list: C525015:PKR1 protein, mouse; D043562:Receptors, G-Protein-Coupled
keywords: genetically altered mice; receptor pharmacology; renal physiology/pathophysiology