title: Transcriptional regulation of organic anion transporting polypeptide SLCO4C1 as a new therapeutic modality to prevent chronic kidney disease.
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.
authors.affiliation: Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Suzuki
authors.forename: Takafumi
authors.initials: T
authors.lastname: Toyohara
authors.forename: Yasutoshi
authors.initials: Y
authors.lastname: Akiyama
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: Eikan
authors.initials: E
authors.lastname: Mishima
authors.forename: Chitose
authors.initials: C
authors.lastname: Suzuki
authors.forename: Sadayoshi
authors.initials: S
authors.lastname: Ito
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Soga
authors.forename: Takaaki
authors.initials: T
authors.lastname: Abe
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D007676:Kidney Failure, Chronic / Q000517:prevention & control*; D027361:Organic Anion Transporters / Q000502:physiology*; D051381:Rats; D014158:Transcription, Genetic
chemical_list: D027361:Organic Anion Transporters; C498174:SLCO4A1 protein, human