Transcriptional regulation of organic anion transporting polypeptide SLCO4C1 as a new therapeutic modality to prevent chronic kidney disease

Takehiro Suzuki, Takafumi Toyohara, Yasutoshi Akiyama, Yoichi Takeuchi, Eikan Mishima, Chitose Suzuki, Sadayoshi Ito, Tomoyoshi Soga, Takaaki Abe

Research output: Contribution to journalReview article

21 Citations (Scopus)

Abstract

Uremic toxins accumulate in patients with chronic kidney diseases (CKDs) and cause further progression of renal damage and cardiovascular diseases. Recently, it was reported that some of the organic anion transporting polypeptides (OATPs) and the organic anion transporters (OATs) are involved in the renal elimination of uremic toxins. SLCO4C1 is the only OATP expressed at the basolateral side of proximal tubular cells in human kidney, and it mediates the excretion of uremic toxins. The overexpression of human SLCO4C1 in rat kidney promotes the renal excretion of uremic toxins and reduces hypertension, cardiomegaly, and renal inflammation in renal failure. Statins induce SLCO4C1 expression thorough transcriptional factor Aryl hydrocarbon receptor through binding of the xenobiotic responsive element at its promoter region. The administration of statin in a rat renal failure model facilitated the elimination of uremic toxins and mitigated organ damage. In addition, metabolomic analysis of rat renal failure models and patients with CKD by capillary electrophoresis-mass spectrometry is a useful method for identifying new uremic solutes and explores surrogate biomarkers for detecting the progression of early stage CKD.

Original languageEnglish
Pages (from-to)3696-3707
Number of pages12
JournalJournal of Pharmaceutical Sciences
Volume100
Issue number9
DOIs
Publication statusPublished - 2011 Jan 1

Keywords

  • ABC transporters
  • Capillary electrophoresis
  • Chronic kidney disease
  • Mass spectrometry
  • Membrane transport
  • Metabolome analysis
  • Organic anion transporter
  • Organic anion-transporting polypeptide transporters
  • Statin
  • Uremic toxin

ASJC Scopus subject areas

  • Pharmaceutical Science

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