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Thick ascending limb‐specific nuclear receptor ERRβ regulates renal ion transports
Author(s) -
Crambert Gilles
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.736.2
Subject(s) - receptor , nephron , endocrinology , medicine , microbiology and biotechnology , kidney , agonist , biology , homeostasis , nuclear receptor , chemistry , transcription factor , biochemistry , gene
Renal functions are regulated to cope with the demands of the organism through activation of different receptors. Among them, the family of the nuclear receptors (NR) participates at the long‐term processes. Identity of the NR expressed in the kidney is known, but their quantitative localization in this ultrastructured organ remained poorly described. Using qPCR on microdissected mouse renal nephronic segments, we established a quantitative expression map of NR along the nephron. This map can serve to identify NR with specific localization. Thus, we unexpectedly found that the estrogen‐related receptor β (ERRβ) is expressed predominantly in the Henle loop (TAL). In vivo treatment with an ERR inverse agonist (diethylstilbestrol) showed a link between this receptor family and the expression of NKCC2, and resulted in phenotype presenting some similarities with the Bartter syndrom (hypokalemia, urinary Na+ loss and volume contraction). We then used a mouse TAL cell line to dissect the mechanisms by which NKCC2 and other transporters are modulated after stimulation of ERRβ with a selective agonist (GSK4716) using CHiP experiments. The TAL segments being involved in the regulation of extracellular volume, blood pressure, Ca2+ and Mg2+ homeostasis, identification of ERRβ as a new regulator of ion transport in this particular segments may contribute to better understand dysfunctions of these parameters.