Ciclosporin reduces paracellin-1 expression and magnesium transport in thick ascending limb cells

Chiz Tzung Chang, Cheng Chieh Hung, Ya Chung Tian, Chih Wei Yang, Mai Szu Wu

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Background. Renal magnesium (Mg 2+) wasting is one of the ciclosporin (CsA) tubular effects. The major site of Mg 2+ transport is the thick ascending limb (TAL), where 70% of the ultrafiltrable Mg 2+ is reabsorbed paracellularly. Paracellin-1 is a tight junction protein, which regulates the paracellular Mg 2+ transport in the TAL. We hypothesize that CsA reduces the expression and function of paracellin-1 and accounts for the observed renal Mg 2+ wasting. Methods. We established an immortalized cultured cortical TAL (cTAL) cell line from L-PK/Tag1 transgenic mice by microdissection. The cultured cells expressed paracellin-1 and the characteristics of cTAL cells. Real-time PCR and western blotting were used to test the CsA effects on paracellin-1 expression of cultured cTAL cells. Cytosolic-free Mg 2+ concentration [Mg 2+] i change with time in a single cTAL cell was used as an indicator of transcellular Mg 2+ transport and assessed by using fluorescence dye Mag-fura-2 AM. Paracellular Mg 2+ transport was measured by cells grown in porous filters. Results. The results showed that CsA significantly reduced paracellin-1 mRNA and protein expression in a dose-dependent manner. CsA (100 ng/ml) incubation for 24 h induced a decrease of paracellin-1 mRNA by 89.4% and paracellin-1 protein by 75.4%. CsA (100 ng/ml) did not change transcellular Mg 2+ transport, but paracellular Mg 2+ transport was decreased in CsA-treated cTAL cells by 74.4%. Conclusion. These results suggested that reduced PCLN-1 expression and paracellular Mg 2+ transport might play a role in the renal Mg 2+ wasting in the CsA tubular effect.

Original languageEnglish
Pages (from-to)1033-1040
Number of pages8
JournalNephrology Dialysis Transplantation
Volume22
Issue number4
DOIs
Publication statusPublished - Apr 1 2007
Externally publishedYes

Keywords

  • Ciclosporin
  • Magnesium transport
  • Paracellin-1
  • PCLN-1
  • Thick ascending limb

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Fingerprint Dive into the research topics of 'Ciclosporin reduces paracellin-1 expression and magnesium transport in thick ascending limb cells'. Together they form a unique fingerprint.

  • Cite this