TY - JOUR
T1 - SLCO4C1 transporter eliminates uremic toxins and attenuates hypertension and renal inflammation
AU - Toyohara, Takafumi
AU - Suzuki, Takehiro
AU - Morimoto, Ryo
AU - Akiyama, Yasutoshi
AU - Souma, Tomokazu
AU - Shiwaku, Hiromi O.
AU - Takeuchi, Yoichi
AU - Mishima, Eikan
AU - Abe, Michiaki
AU - Tanemoto, Masayuki
AU - Masuda, Satohiro
AU - Kawano, Hiroaki
AU - Maemura, Koji
AU - Nakayama, Masaaki
AU - Sato, Hiroshi
AU - Mikkaichi, Tsuyoshi
AU - Yamaguchi, Hiroaki
AU - Fukui, Shigefumi
AU - Fukumoto, Yoshihiro
AU - Shimokawa, Hiroaki
AU - Inui, Ken Ichi
AU - Terasaki, Tetsuya
AU - Goto, Junichi
AU - Ito, Sadayoshi
AU - Hishinuma, Takanori
AU - Rubera, Isabelle
AU - Tauc, Michel
AU - Fujii-Kuriyama, Yoshiaki
AU - Yabuuchi, Hikaru
AU - Moriyama, Yoshinori
AU - Soga, Tomoyoshi
AU - Abe, Takaaki
PY - 2009/12/1
Y1 - 2009/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=72049086464&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=72049086464&partnerID=8YFLogxK
U2 - 10.1681/ASN.2009070696
DO - 10.1681/ASN.2009070696
M3 - Article
C2 - 19875811
AN - SCOPUS:72049086464
SN - 1046-6673
VL - 20
SP - 2546
EP - 2555
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 12
ER -
