title: Effects of a high-sodium diet on renal tubule Ca2+ transporter and claudin expression in Wistar-Kyoto rats.
abstract: BACKGROUND
  Urinary Ca2+ excretion increases with dietary NaCl. NaCl-induced calciuria may be associated with hypertension, urinary stone formation and osteoporosis, but its mechanism and long-term effects are not fully understood. This study examined alterations in the expressions of renal Ca2+ transporters, channels and claudins upon salt loading to better understand the mechanism of salt-induced urinary Ca2+ loss.
  
  
  METHODS
  Eight-week old Wistar-Kyoto rats were fed either 0.3% or 8% NaCl diet for 8 weeks. Renal cortical expressions of Na+/Ca2+ exchanger 1 (NCX1), Ca2+ pump (PCMA1b), Ca2+ channel (TRPV5), calbindin-D28k, and claudins (CLDN-2, -7, -8, -16 and -19) were analyzed by quantitative PCR, western blot and/or immunohistochemistry.
  
  
  RESULTS
  Fractional excretion of Ca2+ increased 6.0 fold with high-salt diet. Renal cortical claudin-2 protein decreased by approximately 20% with decreased immunological staining on tissue sections. Claudin-16 and -19 expressions were not altered. Renal cortical TRPV5, calbindin-D28k and NCX1 expressions increased 1.6, 1.5 and 1.2 fold, respectively.
  
  
  CONCLUSIONS
  Chronic high-salt diet decreased claudin-2 protein and increased renal TRPV5, calbindin-D28k, and NCX1. Salt loading is known to reduce the proximal tubular reabsorption of both Na+ and Ca2+. The reduction in claudin-2 protein expression may be partly responsible for the reduced Ca2+ reabsorption in this segment. The concerted upregulation of more distal Ca2+-transporting molecules may be a physiological response to curtail the loss of Ca2+, although the magnitude of compensation does not seem adequate to bring the urinary Ca2+ excretion down to that of the normal-diet group.
authors.affiliation: Department of Pharmacology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Japan. msasaki@fmu.ac.jp
authors.forename: Midori Sasaki
authors.initials: MS
authors.lastname: Yatabe
authors.forename: Junichi
authors.initials: J
authors.lastname: Yatabe
authors.forename: Kozue
authors.initials: K
authors.lastname: Takano
authors.forename: Yuta
authors.initials: Y
authors.lastname: Murakami
authors.forename: Rina
authors.initials: R
authors.lastname: Sakuta
authors.forename: Sadahiko
authors.initials: S
authors.lastname: Abe
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sanada
authors.forename: Junko
authors.initials: J
authors.lastname: Kimura
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D064092:Calbindin 1; D064026:Calbindins; D002118:Calcium / Q000652:urine; D015220:Calcium Channels / Q000096:biosynthesis*; D062446:Claudin-2 / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D007684:Kidney Tubules / Q000378:metabolism*; D051381:Rats; D011921:Rats, Inbred WKY; D064030:S100 Calcium Binding Protein G / Q000096:biosynthesis*; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage* / Q000009:adverse effects; D019831:Sodium-Calcium Exchanger / Q000096:biosynthesis*; D050916:TRPV Cation Channels / Q000096:biosynthesis*
chemical_list: C576500:Calb1 protein, rat; D064092:Calbindin 1; D064026:Calbindins; D015220:Calcium Channels; D062446:Claudin-2; D064030:S100 Calcium Binding Protein G; D017673:Sodium Chloride, Dietary; D019831:Sodium-Calcium Exchanger; D050916:TRPV Cation Channels; C492241:TRPV5 protein, rat; C110374:sodium-calcium exchanger 1; D002118:Calcium