title: Expression profile of nuclear receptors along male mouse nephron segments reveals a link between ERRβ and thick ascending limb function.
abstract: The nuclear receptor family orchestrates many functions related to reproduction, development, metabolism, and adaptation to the circadian cycle. The majority of these receptors are expressed in the kidney, but their exact quantitative localization in this ultrastructured organ remains poorly described, making it difficult to elucidate the renal function of these receptors. In this report, using quantitative PCR on microdissected mouse renal tubules, we established a detailed quantitative expression map of nuclear receptors along the nephron. This map can serve to identify nuclear receptors with specific localization. Thus, we unexpectedly found that the estrogen-related receptor β (ERRβ) is expressed predominantly in the thick ascending limb (TAL) and, to a much lesser extent, in the distal convoluted tubules. In vivo treatment with an ERR inverse agonist (diethylstilbestrol) showed a link between this receptor family and the expression of the Na⁺,K⁺-2Cl⁻ cotransporter type 2 (NKCC2), and resulted in phenotype presenting some similarities with the Bartter syndrom (hypokalemia, urinary Na⁺ loss and volume contraction). Conversely, stimulation of ERRβ with a selective agonist (GSK4716) in a TAL cell line stimulated NKCC2 expression. All together, these results provide broad information regarding the renal expression of all members of the nuclear receptor family and have allowed us to identify a new regulator of ion transport in the TAL segments.
authors.affiliation: UPMC Univ Paris 6/INSERM/CNRS, Centre de Recherche des Cordeliers, UMRS 872 Equipe 3 Laboratoire de Génomique, Physiologie et Physiopathologie Rénales ERL 7226, Paris, France.
authors.forename: Halla
authors.initials: H
authors.lastname: Krid
authors.forename: Aude
authors.initials: A
authors.lastname: Dorison
authors.forename: Amel
authors.initials: A
authors.lastname: Salhi
authors.forename: Lydie
authors.initials: L
authors.lastname: Cheval
authors.forename: Gilles
authors.initials: G
authors.lastname: Crambert
mesh_terms: D000818:Animals; D015153:Blotting, Western; D047629:Estrogen Receptor beta / Q000378:metabolism*; D020869:Gene Expression Profiling; D008297:Male; D051379:Mice; D009399:Nephrons / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D047629:Estrogen Receptor beta; D018160:Receptors, Cytoplasmic and Nuclear