SLCO4C1 Transporter Eliminates Uremic Toxins and Attenuates Hypertension and Renal Inflammation
書誌事項
- 公開日
- 2009-12
- DOI
-
- 10.1681/asn.2009070696
- 公開者
- Ovid Technologies (Wolters Kluwer Health)
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説明
Hypertension in patients with chronic kidney disease (CKD) strongly associates with cardiovascular events. Among patients with CKD, reducing the accumulation of uremic toxins may protect against the development of hypertension and progression of renal damage, but there are no established therapies to accomplish this. Here, overexpression of human kidney-specific organic anion transporter SLCO4C1 in rat kidney reduced hypertension, cardiomegaly, and inflammation in the setting of renal failure. In addition, SLCO4C1 overexpression decreased plasma levels of the uremic toxins guanidino succinate, asymmetric dimethylarginine, and the newly identified trans-aconitate. We found that xenobiotic responsive element core motifs regulate SLCO4C1 transcription, and various statins, which act as inducers of nuclear aryl hydrocarbon receptors, upregulate SLCO4C1 transcription. Pravastatin, which is cardioprotective, increased the clearance of asymmetric dimethylarginine and trans-aconitate in renal failure. These data suggest that drugs that upregulate SLCO4C1 may have therapeutic potential for patients with CKD.
収録刊行物
-
- Journal of the American Society of Nephrology
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Journal of the American Society of Nephrology 20 (12), 2546-2555, 2009-12
Ovid Technologies (Wolters Kluwer Health)
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キーワード
- Male
- Nephritis
- Base Sequence
- [SDV]Life Sciences [q-bio]
- Molecular Sequence Data
- Biological Transport, Active
- Gene Expression
- Organic Anion Transporters
- DNA
- Models, Biological
- Recombinant Proteins
- Rats
- Animals, Genetically Modified
- Hypertension
- Animals
- Humans
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Renal Insufficiency, Chronic
- Promoter Regions, Genetic
- Toxins, Biological
- Uremia
