Indoxyl sulfate enhances p53-tgf-β1-smad3 pathway in proximal tubular cells

American Journal of Nephrology

Volumn 37, Issue 2, 2013, Pages 97-103

  Shimizu, Hidehisa ^a   Yisireyili, Maimaiti ^a   Nishijima, Fuyuhiko ^b   Niwa, Toshimitsu ^a  

^a NAGOYA UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

^b KUREHA CORPORATION   (Japan)

Author keywords

Smooth muscle actin; Chronic kidney disease; Extracellular signal regulated kinase; p53; Uremic toxin

Indexed keywords

1,4 DIAMINO 1,4 BIS(2 AMINOPHENYLTHIO) 2,3 DICYANOBUTADIENE; ALPHA SMOOTH MUSCLE ACTIN; INDICAN; MITOGEN ACTIVATED PROTEIN KINASE; NUTLIN 3; PIFITHRIN ALPHA; PROTEIN P53; SMAD3 PROTEIN; TRANSFORMING GROWTH FACTOR BETA1; MESSENGER RNA;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; DAHL SALT SENSITIVE RAT; DRUG EFFECT; IMMUNOHISTOCHEMISTRY; IN VIVO STUDY; KIDNEY TUBULE CELL; MALE; MOLECULAR INTERACTION; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; RAT; SIGNAL TRANSDUCTION; CONTROLLED STUDY; ENZYME PHOSPHORYLATION; HEMODIALYSIS; HUMAN; HUMAN CELL; KIDNEY PROXIMAL TUBULE; PROTEIN PROTEIN INTERACTION; REAL TIME POLYMERASE CHAIN REACTION; UPREGULATION; WESTERN BLOTTING;

ACTINS; ANALYSIS OF VARIANCE; ANIMALS; BENZOTHIAZOLES; CELLS, CULTURED; EXTRACELLULAR SIGNAL-REGULATED MAP KINASES; HUMANS; IMIDAZOLES; INDICAN; KIDNEY TUBULES, PROXIMAL; MALE; PHOSPHORYLATION; PIPERAZINES; RATS; RATS, INBRED DAHL; RNA, MESSENGER; SIGNAL TRANSDUCTION; SMAD3 PROTEIN; TOLUENE; TRANSFORMING GROWTH FACTOR BETA1; TUMOR SUPPRESSOR PROTEIN P53; UP-REGULATION;

EID: 84873030568     PISSN: 02508095     EISSN: 14219670     Source Type: Journal    
DOI: 10.1159/000346420     Document Type: Article

References (18)

1. Niwa T, Ise M: Indoxyl sulfate, a circulating uremic toxin, stimulates the progression of glomerular sclerosis. J Lab Clin Med 1994; 124: 96-104.
2. Niwa T, Ise M, Miyazaki T: Progression of glomerular sclerosis in experimental uremic rats by administration of indole, a precursor of indoxyl sulfate. Am J Nephrol 1994; 14: 207-212.
3. Miyazaki T, Ise M, Seo H, Niwa T: Indoxyl sulfate increases the gene expressions of TGF- 1, TIMP-1 and pro-1(I)collagen in uremic rat kidneys. Kidney Int Suppl 1997; 62:S15-S22.
4. Bolati D, Shimizu H, Higashiyama Y, Nishijima F, Niwa T: Indoxyl sulfate induces epithelial- to-mesenchymal transition in rat kidneys and human proximal tubular cells. Am J Nephrol 2011; 34: 318-323.
5. Enomoto A, Takeda M, Tojo A, Sekine T, Cha SH, Khamdang S, Takayama F, Aoyama I, Nakamura S, Endou H, Niwa T: Role of organic anion transporters in the tubular transport of indoxyl sulfate and the induction of its nephrotoxicity. J Am Soc Nephrol 2002; 13: 1711-1720.
6. Shimizu H, Bolati D, Adijiang A, Enomoto A, Nishijima F, Dateki M, Niwa T: Senescence and dysfunction of proximal tubular cells are associated with activated p53 expression by indoxyl sulfate. Am J Physiol Cell Physiol 2010; 299:C1110-C1117.
7. Shimizu H, Bolati D, Adijiang A, Muteliefu G, Enomoto A, Nishijima F, Dateki M, Niwa T: NF-B plays an important role in indoxyl sulfate-induced cellular senescence, fibrotic gene expression, and inhibition of proliferation in proximal tubular cells. Am J Physiol Cell Physiol 2011; 301:C1201-C1212.
8. Shimizu H, Bolati D, Adijiang A, Adelibieke Y, Muteliefu G, Enomoto A, Higashiyama Y, Higuchi Y, Nishijima F, Niwa T: Indoxyl sulfate downregulates renal expression of Klotho through production of ROS and activation of nuclear factor-B. Am J Nephrol 2011; 33: 319-324.
9. Iwano M, Neilson EG: Mechanisms of tubulointerstitial fibrosis. Curr Opin Nephrol Hypertens 2004; 13: 279-284.
10. Sato M, Muragaki Y, Saika S, Roberts AB, Ooshima A: Targeted disruption of TGF-1 / Smad3 signaling protects against renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction. J Clin Invest 2003; 112: 1486-1494.
11. Derynck R, Gelbart WM, Harland RM, Heldin CH, Kern SE, Massagué J, Melton DA, Mlodzik M, Padgett RW, Roberts AB, Smith J, Thomsen GH, Vogelstein B, Wang XF: Nomenclature: vertebrate mediators of TGF-family signals. Cell 1996; 87: 173.
12. Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, Kong N, Kammlott U, Lukacs C, Klein C, Fotouhi N, Liu EA: In vivo activation of the p53 pathway by smallmolecule antagonists of MDM2. Science 2004; 303: 844-848.
13. Shimizu H, Bolati D, Higashiyama Y, Nishijima F, Shimizu K, Niwa T: Indoxyl sulfate upregulates renal expression of MCP-1 via production of ROS and activation of NF-B, p53, ERK, and JNK in proximal tubular cells. Life Sci 2012; 90: 525-530.
14. Ross KR, Corey DA, Dunn JM, Kelley TJ: SMAD3 expression is regulated by mitogenactivated protein kinase kinase-1 in epithelial and smooth muscle cells. Cell Signal 2007; 19: 923-931.
15. Doi S, Zou Y, Togao O, Pastor JV, John GB, Wang L, Shiizaki K, Gotschall R, Schiavi S, Yorioka N, Takahashi M, Boothman DA, Kuro-o M: Klotho inhibits transforming growth factor-1 signaling and suppresses renal fibrosis and cancer metastasis in mice. J Biol Chem 2011; 286: 8655-8665.
16. Niwa T: Therapeutic removal of uremic toxins by oral sorbent; in Niwa T (ed): Uremic Toxins. Hoboken/NJ, Wiley, 2012, pp 359- 371.
17. Bolati D, Shimizu H, Niwa T: AST-120 ameliorates epithelial-to- mesenchymal transition and interstitial fibrosis in the kidneys of chronic kidney disease rats. J Ren Nutr 2012; 22: 176-180.
18. Adijiang A, Niwa T: An oral sorbent, AST- 120, increases Klotho expression and inhibits cell senescence in the kidney of uremic rats. Am J Nephrol 2010; 31: 160-164.