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SLCO4C1 transporter eliminates uremic toxins and attenuates hypertension and renal inflammation.

Publication ,  Journal Article
Toyohara, T; Suzuki, T; Morimoto, R; Akiyama, Y; Souma, T; Shiwaku, HO; Takeuchi, Y; Mishima, E; Abe, M; Tanemoto, M; Masuda, S; Kawano, H ...
Published in: J Am Soc Nephrol
December 2009

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.

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Published In

J Am Soc Nephrol

DOI

EISSN

1533-3450

Publication Date

December 2009

Volume

20

Issue

12

Start / End Page

2546 / 2555

Location

United States

Related Subject Headings

  • Urology & Nephrology
  • Uremia
  • Toxins, Biological
  • Renal Insufficiency, Chronic
  • Recombinant Proteins
  • Rats
  • Promoter Regions, Genetic
  • Organic Anion Transporters
  • Nephritis
  • Molecular Sequence Data
 

Citation

APA
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Toyohara, T., Suzuki, T., Morimoto, R., Akiyama, Y., Souma, T., Shiwaku, H. O., … Abe, T. (2009). SLCO4C1 transporter eliminates uremic toxins and attenuates hypertension and renal inflammation. J Am Soc Nephrol, 20(12), 2546–2555. https://doi.org/10.1681/ASN.2009070696
Toyohara, Takafumi, Takehiro Suzuki, Ryo Morimoto, Yasutoshi Akiyama, Tomokazu Souma, Hiromi O. Shiwaku, Yoichi Takeuchi, et al. “SLCO4C1 transporter eliminates uremic toxins and attenuates hypertension and renal inflammation.J Am Soc Nephrol 20, no. 12 (December 2009): 2546–55. https://doi.org/10.1681/ASN.2009070696.
Toyohara T, Suzuki T, Morimoto R, Akiyama Y, Souma T, Shiwaku HO, et al. SLCO4C1 transporter eliminates uremic toxins and attenuates hypertension and renal inflammation. J Am Soc Nephrol. 2009 Dec;20(12):2546–55.
Toyohara, Takafumi, et al. “SLCO4C1 transporter eliminates uremic toxins and attenuates hypertension and renal inflammation.J Am Soc Nephrol, vol. 20, no. 12, Dec. 2009, pp. 2546–55. Pubmed, doi:10.1681/ASN.2009070696.
Toyohara T, Suzuki T, Morimoto R, Akiyama Y, Souma T, Shiwaku HO, Takeuchi Y, Mishima E, Abe M, Tanemoto M, Masuda S, Kawano H, Maemura K, Nakayama M, Sato H, Mikkaichi T, Yamaguchi H, Fukui S, Fukumoto Y, Shimokawa H, Inui K-I, Terasaki T, Goto J, Ito S, Hishinuma T, Rubera I, Tauc M, Fujii-Kuriyama Y, Yabuuchi H, Moriyama Y, Soga T, Abe T. SLCO4C1 transporter eliminates uremic toxins and attenuates hypertension and renal inflammation. J Am Soc Nephrol. 2009 Dec;20(12):2546–2555.

Published In

J Am Soc Nephrol

DOI

EISSN

1533-3450

Publication Date

December 2009

Volume

20

Issue

12

Start / End Page

2546 / 2555

Location

United States

Related Subject Headings

  • Urology & Nephrology
  • Uremia
  • Toxins, Biological
  • Renal Insufficiency, Chronic
  • Recombinant Proteins
  • Rats
  • Promoter Regions, Genetic
  • Organic Anion Transporters
  • Nephritis
  • Molecular Sequence Data