Indoxyl sulfate down-regulates SLCO4C1 transporter through up-regulation of GATA3.

The accumulated uremic toxins inhibit the expression of various renal transporters and this inhibition may further reduce renal function and subsequently cause the accumulation of uremic toxins. However, the precise mechanism of the nephrotoxicity of uremic toxins on renal transport has been poorly...
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Autor*in:	Yasutoshi Akiyama [verfasserIn] Koichi Kikuchi [verfasserIn] Daisuke Saigusa [verfasserIn] Takehiro Suzuki [verfasserIn] Yoichi Takeuchi [verfasserIn] Eikan Mishima [verfasserIn] Yasuaki Yamamoto [verfasserIn] Ayako Ishida [verfasserIn] Daiki Sugawara [verfasserIn] Daisuke Jinno [verfasserIn] Hisato Shima [verfasserIn] Takafumi Toyohara [verfasserIn] Chitose Suzuki [verfasserIn] Tomokazu Souma [verfasserIn] Takashi Moriguchi [verfasserIn] Yoshihisa Tomioka [verfasserIn] Sadayoshi Ito [verfasserIn] Takaaki Abe [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2013

Übergeordnetes Werk:	In: PLoS ONE - Public Library of Science (PLoS), 2007, 8(2013), 7, p e66518
Übergeordnetes Werk:	volume:8 ; year:2013 ; number:7, p e66518

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1371/journal.pone.0066518

Katalog-ID:	DOAJ01320811X

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allfields	10.1371/journal.pone.0066518 doi (DE-627)DOAJ01320811X (DE-599)DOAJ67d2927e869f4cfaba44d2471a1ab951 DE-627 ger DE-627 rakwb eng Yasutoshi Akiyama verfasserin aut Indoxyl sulfate down-regulates SLCO4C1 transporter through up-regulation of GATA3. 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The accumulated uremic toxins inhibit the expression of various renal transporters and this inhibition may further reduce renal function and subsequently cause the accumulation of uremic toxins. However, the precise mechanism of the nephrotoxicity of uremic toxins on renal transport has been poorly understood. Here we report that indoxyl sulfate, one of the potent uremic toxins, directly suppresses the renal-specific organic anion transporter SLCO4C1 expression through a transcription factor GATA3. The promoter region of SLCO4C1 gene has several GATA motifs, and indoxyl sulfate up-regulated GATA3 mRNA and subsequently down-regulated SLCO4C1 mRNA. Overexpression of GATA3 significantly reduced SLCO4C1 expression, and silencing of GATA3 increased SLCO4C1 expression vice versa. Administration of indoxyl sulfate in rats reduced renal expression of slco4c1 and under this condition, plasma level of guanidinosuccinate, one of the preferable substrates of slco4c1, was significantly increased without changing plasma creatinine. Furthermore, in 5/6 nephrectomized rats, treatment with oral adsorbent AST-120 significantly decreased plasma indoxyl sulfate level and conversely increased the expression of slco4c1, following the reduction of plasma level of guanidinosuccinate. These data suggest that the removal of indoxyl sulfate and blocking its signal pathway may help to restore the SLCO4C1-mediated renal excretion of uremic toxins in CKD. Medicine R Science Q Koichi Kikuchi verfasserin aut Daisuke Saigusa verfasserin aut Takehiro Suzuki verfasserin aut Yoichi Takeuchi verfasserin aut Eikan Mishima verfasserin aut Yasuaki Yamamoto verfasserin aut Ayako Ishida verfasserin aut Daiki Sugawara verfasserin aut Daisuke Jinno verfasserin aut Hisato Shima verfasserin aut Takafumi Toyohara verfasserin aut Chitose Suzuki verfasserin aut Tomokazu Souma verfasserin aut Takashi Moriguchi verfasserin aut Yoshihisa Tomioka verfasserin aut Sadayoshi Ito verfasserin aut Takaaki Abe verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 8(2013), 7, p e66518 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:8 year:2013 number:7, p e66518 https://doi.org/10.1371/journal.pone.0066518 kostenfrei https://doaj.org/article/67d2927e869f4cfaba44d2471a1ab951 kostenfrei http://europepmc.org/articles/PMC3706553?pdf=render kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2013 7, p e66518
spelling	10.1371/journal.pone.0066518 doi (DE-627)DOAJ01320811X (DE-599)DOAJ67d2927e869f4cfaba44d2471a1ab951 DE-627 ger DE-627 rakwb eng Yasutoshi Akiyama verfasserin aut Indoxyl sulfate down-regulates SLCO4C1 transporter through up-regulation of GATA3. 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The accumulated uremic toxins inhibit the expression of various renal transporters and this inhibition may further reduce renal function and subsequently cause the accumulation of uremic toxins. However, the precise mechanism of the nephrotoxicity of uremic toxins on renal transport has been poorly understood. Here we report that indoxyl sulfate, one of the potent uremic toxins, directly suppresses the renal-specific organic anion transporter SLCO4C1 expression through a transcription factor GATA3. The promoter region of SLCO4C1 gene has several GATA motifs, and indoxyl sulfate up-regulated GATA3 mRNA and subsequently down-regulated SLCO4C1 mRNA. Overexpression of GATA3 significantly reduced SLCO4C1 expression, and silencing of GATA3 increased SLCO4C1 expression vice versa. Administration of indoxyl sulfate in rats reduced renal expression of slco4c1 and under this condition, plasma level of guanidinosuccinate, one of the preferable substrates of slco4c1, was significantly increased without changing plasma creatinine. Furthermore, in 5/6 nephrectomized rats, treatment with oral adsorbent AST-120 significantly decreased plasma indoxyl sulfate level and conversely increased the expression of slco4c1, following the reduction of plasma level of guanidinosuccinate. These data suggest that the removal of indoxyl sulfate and blocking its signal pathway may help to restore the SLCO4C1-mediated renal excretion of uremic toxins in CKD. Medicine R Science Q Koichi Kikuchi verfasserin aut Daisuke Saigusa verfasserin aut Takehiro Suzuki verfasserin aut Yoichi Takeuchi verfasserin aut Eikan Mishima verfasserin aut Yasuaki Yamamoto verfasserin aut Ayako Ishida verfasserin aut Daiki Sugawara verfasserin aut Daisuke Jinno verfasserin aut Hisato Shima verfasserin aut Takafumi Toyohara verfasserin aut Chitose Suzuki verfasserin aut Tomokazu Souma verfasserin aut Takashi Moriguchi verfasserin aut Yoshihisa Tomioka verfasserin aut Sadayoshi Ito verfasserin aut Takaaki Abe verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 8(2013), 7, p e66518 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:8 year:2013 number:7, p e66518 https://doi.org/10.1371/journal.pone.0066518 kostenfrei https://doaj.org/article/67d2927e869f4cfaba44d2471a1ab951 kostenfrei http://europepmc.org/articles/PMC3706553?pdf=render kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2013 7, p e66518
allfields_unstemmed	10.1371/journal.pone.0066518 doi (DE-627)DOAJ01320811X (DE-599)DOAJ67d2927e869f4cfaba44d2471a1ab951 DE-627 ger DE-627 rakwb eng Yasutoshi Akiyama verfasserin aut Indoxyl sulfate down-regulates SLCO4C1 transporter through up-regulation of GATA3. 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The accumulated uremic toxins inhibit the expression of various renal transporters and this inhibition may further reduce renal function and subsequently cause the accumulation of uremic toxins. However, the precise mechanism of the nephrotoxicity of uremic toxins on renal transport has been poorly understood. Here we report that indoxyl sulfate, one of the potent uremic toxins, directly suppresses the renal-specific organic anion transporter SLCO4C1 expression through a transcription factor GATA3. The promoter region of SLCO4C1 gene has several GATA motifs, and indoxyl sulfate up-regulated GATA3 mRNA and subsequently down-regulated SLCO4C1 mRNA. Overexpression of GATA3 significantly reduced SLCO4C1 expression, and silencing of GATA3 increased SLCO4C1 expression vice versa. Administration of indoxyl sulfate in rats reduced renal expression of slco4c1 and under this condition, plasma level of guanidinosuccinate, one of the preferable substrates of slco4c1, was significantly increased without changing plasma creatinine. Furthermore, in 5/6 nephrectomized rats, treatment with oral adsorbent AST-120 significantly decreased plasma indoxyl sulfate level and conversely increased the expression of slco4c1, following the reduction of plasma level of guanidinosuccinate. These data suggest that the removal of indoxyl sulfate and blocking its signal pathway may help to restore the SLCO4C1-mediated renal excretion of uremic toxins in CKD. Medicine R Science Q Koichi Kikuchi verfasserin aut Daisuke Saigusa verfasserin aut Takehiro Suzuki verfasserin aut Yoichi Takeuchi verfasserin aut Eikan Mishima verfasserin aut Yasuaki Yamamoto verfasserin aut Ayako Ishida verfasserin aut Daiki Sugawara verfasserin aut Daisuke Jinno verfasserin aut Hisato Shima verfasserin aut Takafumi Toyohara verfasserin aut Chitose Suzuki verfasserin aut Tomokazu Souma verfasserin aut Takashi Moriguchi verfasserin aut Yoshihisa Tomioka verfasserin aut Sadayoshi Ito verfasserin aut Takaaki Abe verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 8(2013), 7, p e66518 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:8 year:2013 number:7, p e66518 https://doi.org/10.1371/journal.pone.0066518 kostenfrei https://doaj.org/article/67d2927e869f4cfaba44d2471a1ab951 kostenfrei http://europepmc.org/articles/PMC3706553?pdf=render kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2013 7, p e66518
allfieldsGer	10.1371/journal.pone.0066518 doi (DE-627)DOAJ01320811X (DE-599)DOAJ67d2927e869f4cfaba44d2471a1ab951 DE-627 ger DE-627 rakwb eng Yasutoshi Akiyama verfasserin aut Indoxyl sulfate down-regulates SLCO4C1 transporter through up-regulation of GATA3. 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The accumulated uremic toxins inhibit the expression of various renal transporters and this inhibition may further reduce renal function and subsequently cause the accumulation of uremic toxins. However, the precise mechanism of the nephrotoxicity of uremic toxins on renal transport has been poorly understood. Here we report that indoxyl sulfate, one of the potent uremic toxins, directly suppresses the renal-specific organic anion transporter SLCO4C1 expression through a transcription factor GATA3. The promoter region of SLCO4C1 gene has several GATA motifs, and indoxyl sulfate up-regulated GATA3 mRNA and subsequently down-regulated SLCO4C1 mRNA. Overexpression of GATA3 significantly reduced SLCO4C1 expression, and silencing of GATA3 increased SLCO4C1 expression vice versa. Administration of indoxyl sulfate in rats reduced renal expression of slco4c1 and under this condition, plasma level of guanidinosuccinate, one of the preferable substrates of slco4c1, was significantly increased without changing plasma creatinine. Furthermore, in 5/6 nephrectomized rats, treatment with oral adsorbent AST-120 significantly decreased plasma indoxyl sulfate level and conversely increased the expression of slco4c1, following the reduction of plasma level of guanidinosuccinate. These data suggest that the removal of indoxyl sulfate and blocking its signal pathway may help to restore the SLCO4C1-mediated renal excretion of uremic toxins in CKD. Medicine R Science Q Koichi Kikuchi verfasserin aut Daisuke Saigusa verfasserin aut Takehiro Suzuki verfasserin aut Yoichi Takeuchi verfasserin aut Eikan Mishima verfasserin aut Yasuaki Yamamoto verfasserin aut Ayako Ishida verfasserin aut Daiki Sugawara verfasserin aut Daisuke Jinno verfasserin aut Hisato Shima verfasserin aut Takafumi Toyohara verfasserin aut Chitose Suzuki verfasserin aut Tomokazu Souma verfasserin aut Takashi Moriguchi verfasserin aut Yoshihisa Tomioka verfasserin aut Sadayoshi Ito verfasserin aut Takaaki Abe verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 8(2013), 7, p e66518 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:8 year:2013 number:7, p e66518 https://doi.org/10.1371/journal.pone.0066518 kostenfrei https://doaj.org/article/67d2927e869f4cfaba44d2471a1ab951 kostenfrei http://europepmc.org/articles/PMC3706553?pdf=render kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2013 7, p e66518
allfieldsSound	10.1371/journal.pone.0066518 doi (DE-627)DOAJ01320811X (DE-599)DOAJ67d2927e869f4cfaba44d2471a1ab951 DE-627 ger DE-627 rakwb eng Yasutoshi Akiyama verfasserin aut Indoxyl sulfate down-regulates SLCO4C1 transporter through up-regulation of GATA3. 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The accumulated uremic toxins inhibit the expression of various renal transporters and this inhibition may further reduce renal function and subsequently cause the accumulation of uremic toxins. However, the precise mechanism of the nephrotoxicity of uremic toxins on renal transport has been poorly understood. Here we report that indoxyl sulfate, one of the potent uremic toxins, directly suppresses the renal-specific organic anion transporter SLCO4C1 expression through a transcription factor GATA3. The promoter region of SLCO4C1 gene has several GATA motifs, and indoxyl sulfate up-regulated GATA3 mRNA and subsequently down-regulated SLCO4C1 mRNA. Overexpression of GATA3 significantly reduced SLCO4C1 expression, and silencing of GATA3 increased SLCO4C1 expression vice versa. Administration of indoxyl sulfate in rats reduced renal expression of slco4c1 and under this condition, plasma level of guanidinosuccinate, one of the preferable substrates of slco4c1, was significantly increased without changing plasma creatinine. Furthermore, in 5/6 nephrectomized rats, treatment with oral adsorbent AST-120 significantly decreased plasma indoxyl sulfate level and conversely increased the expression of slco4c1, following the reduction of plasma level of guanidinosuccinate. These data suggest that the removal of indoxyl sulfate and blocking its signal pathway may help to restore the SLCO4C1-mediated renal excretion of uremic toxins in CKD. Medicine R Science Q Koichi Kikuchi verfasserin aut Daisuke Saigusa verfasserin aut Takehiro Suzuki verfasserin aut Yoichi Takeuchi verfasserin aut Eikan Mishima verfasserin aut Yasuaki Yamamoto verfasserin aut Ayako Ishida verfasserin aut Daiki Sugawara verfasserin aut Daisuke Jinno verfasserin aut Hisato Shima verfasserin aut Takafumi Toyohara verfasserin aut Chitose Suzuki verfasserin aut Tomokazu Souma verfasserin aut Takashi Moriguchi verfasserin aut Yoshihisa Tomioka verfasserin aut Sadayoshi Ito verfasserin aut Takaaki Abe verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 8(2013), 7, p e66518 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:8 year:2013 number:7, p e66518 https://doi.org/10.1371/journal.pone.0066518 kostenfrei https://doaj.org/article/67d2927e869f4cfaba44d2471a1ab951 kostenfrei http://europepmc.org/articles/PMC3706553?pdf=render kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2013 7, p e66518
language	English
source	In PLoS ONE 8(2013), 7, p e66518 volume:8 year:2013 number:7, p e66518
sourceStr	In PLoS ONE 8(2013), 7, p e66518 volume:8 year:2013 number:7, p e66518
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Medicine R Science Q
isfreeaccess_bool	true
container_title	PLoS ONE
authorswithroles_txt_mv	Yasutoshi Akiyama @@aut@@ Koichi Kikuchi @@aut@@ Daisuke Saigusa @@aut@@ Takehiro Suzuki @@aut@@ Yoichi Takeuchi @@aut@@ Eikan Mishima @@aut@@ Yasuaki Yamamoto @@aut@@ Ayako Ishida @@aut@@ Daiki Sugawara @@aut@@ Daisuke Jinno @@aut@@ Hisato Shima @@aut@@ Takafumi Toyohara @@aut@@ Chitose Suzuki @@aut@@ Tomokazu Souma @@aut@@ Takashi Moriguchi @@aut@@ Yoshihisa Tomioka @@aut@@ Sadayoshi Ito @@aut@@ Takaaki Abe @@aut@@
publishDateDaySort_date	2013-01-01T00:00:00Z
hierarchy_top_id	523574592
id	DOAJ01320811X
language_de	englisch
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author	Yasutoshi Akiyama
spellingShingle	Yasutoshi Akiyama misc Medicine misc R misc Science misc Q Indoxyl sulfate down-regulates SLCO4C1 transporter through up-regulation of GATA3.
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topic_title	Indoxyl sulfate down-regulates SLCO4C1 transporter through up-regulation of GATA3
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title	Indoxyl sulfate down-regulates SLCO4C1 transporter through up-regulation of GATA3.
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title_full	Indoxyl sulfate down-regulates SLCO4C1 transporter through up-regulation of GATA3
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author_browse	Yasutoshi Akiyama Koichi Kikuchi Daisuke Saigusa Takehiro Suzuki Yoichi Takeuchi Eikan Mishima Yasuaki Yamamoto Ayako Ishida Daiki Sugawara Daisuke Jinno Hisato Shima Takafumi Toyohara Chitose Suzuki Tomokazu Souma Takashi Moriguchi Yoshihisa Tomioka Sadayoshi Ito Takaaki Abe
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title_sort	indoxyl sulfate down-regulates slco4c1 transporter through up-regulation of gata3
title_auth	Indoxyl sulfate down-regulates SLCO4C1 transporter through up-regulation of GATA3.
abstract	The accumulated uremic toxins inhibit the expression of various renal transporters and this inhibition may further reduce renal function and subsequently cause the accumulation of uremic toxins. However, the precise mechanism of the nephrotoxicity of uremic toxins on renal transport has been poorly understood. Here we report that indoxyl sulfate, one of the potent uremic toxins, directly suppresses the renal-specific organic anion transporter SLCO4C1 expression through a transcription factor GATA3. The promoter region of SLCO4C1 gene has several GATA motifs, and indoxyl sulfate up-regulated GATA3 mRNA and subsequently down-regulated SLCO4C1 mRNA. Overexpression of GATA3 significantly reduced SLCO4C1 expression, and silencing of GATA3 increased SLCO4C1 expression vice versa. Administration of indoxyl sulfate in rats reduced renal expression of slco4c1 and under this condition, plasma level of guanidinosuccinate, one of the preferable substrates of slco4c1, was significantly increased without changing plasma creatinine. Furthermore, in 5/6 nephrectomized rats, treatment with oral adsorbent AST-120 significantly decreased plasma indoxyl sulfate level and conversely increased the expression of slco4c1, following the reduction of plasma level of guanidinosuccinate. These data suggest that the removal of indoxyl sulfate and blocking its signal pathway may help to restore the SLCO4C1-mediated renal excretion of uremic toxins in CKD.
abstractGer	The accumulated uremic toxins inhibit the expression of various renal transporters and this inhibition may further reduce renal function and subsequently cause the accumulation of uremic toxins. However, the precise mechanism of the nephrotoxicity of uremic toxins on renal transport has been poorly understood. Here we report that indoxyl sulfate, one of the potent uremic toxins, directly suppresses the renal-specific organic anion transporter SLCO4C1 expression through a transcription factor GATA3. The promoter region of SLCO4C1 gene has several GATA motifs, and indoxyl sulfate up-regulated GATA3 mRNA and subsequently down-regulated SLCO4C1 mRNA. Overexpression of GATA3 significantly reduced SLCO4C1 expression, and silencing of GATA3 increased SLCO4C1 expression vice versa. Administration of indoxyl sulfate in rats reduced renal expression of slco4c1 and under this condition, plasma level of guanidinosuccinate, one of the preferable substrates of slco4c1, was significantly increased without changing plasma creatinine. Furthermore, in 5/6 nephrectomized rats, treatment with oral adsorbent AST-120 significantly decreased plasma indoxyl sulfate level and conversely increased the expression of slco4c1, following the reduction of plasma level of guanidinosuccinate. These data suggest that the removal of indoxyl sulfate and blocking its signal pathway may help to restore the SLCO4C1-mediated renal excretion of uremic toxins in CKD.
abstract_unstemmed	The accumulated uremic toxins inhibit the expression of various renal transporters and this inhibition may further reduce renal function and subsequently cause the accumulation of uremic toxins. However, the precise mechanism of the nephrotoxicity of uremic toxins on renal transport has been poorly understood. Here we report that indoxyl sulfate, one of the potent uremic toxins, directly suppresses the renal-specific organic anion transporter SLCO4C1 expression through a transcription factor GATA3. The promoter region of SLCO4C1 gene has several GATA motifs, and indoxyl sulfate up-regulated GATA3 mRNA and subsequently down-regulated SLCO4C1 mRNA. Overexpression of GATA3 significantly reduced SLCO4C1 expression, and silencing of GATA3 increased SLCO4C1 expression vice versa. Administration of indoxyl sulfate in rats reduced renal expression of slco4c1 and under this condition, plasma level of guanidinosuccinate, one of the preferable substrates of slco4c1, was significantly increased without changing plasma creatinine. Furthermore, in 5/6 nephrectomized rats, treatment with oral adsorbent AST-120 significantly decreased plasma indoxyl sulfate level and conversely increased the expression of slco4c1, following the reduction of plasma level of guanidinosuccinate. These data suggest that the removal of indoxyl sulfate and blocking its signal pathway may help to restore the SLCO4C1-mediated renal excretion of uremic toxins in CKD.
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title_short	Indoxyl sulfate down-regulates SLCO4C1 transporter through up-regulation of GATA3.
url	https://doi.org/10.1371/journal.pone.0066518 https://doaj.org/article/67d2927e869f4cfaba44d2471a1ab951 http://europepmc.org/articles/PMC3706553?pdf=render https://doaj.org/toc/1932-6203
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Indoxyl sulfate down-regulates SLCO4C1 transporter through up-regulation of GATA3.

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