TY - JOUR
T1 - P-Cresol sulfate and indoxyl sulfate induce similar cellular inflammatory gene expressions in cultured proximal renal tubular cells
AU - Sun, Chiao Yin
AU - Hsu, Hsiang Hao
AU - Wu, Mai-Szu
N1 - Funding Information:
Acknowledgements. This study was supported by a research grant from the National Science Council (NMRPD190361). We would like to thank the Kureha Corporation (Japan) for providing PCS. We would like to express our appreciation to Dr Alain Vandewalle (Inserm Unit U773, Faculté de Médecine Xavier Bichat, 75870, Paris) for providing the cultured PKSV cells. We also would like to thank the staff from the medical research center of Keelung Chang Gung Memorial Hospital for their assistance in this study.
PY - 2013/1
Y1 - 2013/1
N2 - Backgroundp-Cresol sulfate (PCS) and indoxyl sulfate (IS) have important roles in the kidney injury. The aim of this study was to determine the inflammatory response to PCS and IS.MethodsCultured mouse proximal renal tubular cells were treated with PCS or IS and analyzed by polymerase chain reaction array with an inflammation and immune panel. Gene annotation enrichment and functional annotation clustering were analyzed with the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Functional networks of the target genes were analyzed with the algorithm GeneMANIA. Results PCS and IS increased the expression of inflammation associated genes. Sixteen upregulated gene clusters of cells treated with PCS or IS were found. The major cytokines in the functional networks generated by PCS or IS treatment were Tgfb1, Fasl, Il6/15, Il15, Csf1/3 and Cxcl10. The major intracellular signal triggered by PCS or IS included Stats, Smads, Nfkb2, Ikbkb, Bcl2 and Bax. In both PCS-and IS-treated cells, Col4a5, Cxc10, Fasl, Stat1 and Ikbkb were the target genes in the predicted molecular functional networks connected to Tgfb1.ConclusionsPCS and IS stimulate significant cellular inflammation. Similar immune and cellular inflammatory responses were induced by PCS or IS on cultured proximal renal tubular cells.
AB - Backgroundp-Cresol sulfate (PCS) and indoxyl sulfate (IS) have important roles in the kidney injury. The aim of this study was to determine the inflammatory response to PCS and IS.MethodsCultured mouse proximal renal tubular cells were treated with PCS or IS and analyzed by polymerase chain reaction array with an inflammation and immune panel. Gene annotation enrichment and functional annotation clustering were analyzed with the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Functional networks of the target genes were analyzed with the algorithm GeneMANIA. Results PCS and IS increased the expression of inflammation associated genes. Sixteen upregulated gene clusters of cells treated with PCS or IS were found. The major cytokines in the functional networks generated by PCS or IS treatment were Tgfb1, Fasl, Il6/15, Il15, Csf1/3 and Cxcl10. The major intracellular signal triggered by PCS or IS included Stats, Smads, Nfkb2, Ikbkb, Bcl2 and Bax. In both PCS-and IS-treated cells, Col4a5, Cxc10, Fasl, Stat1 and Ikbkb were the target genes in the predicted molecular functional networks connected to Tgfb1.ConclusionsPCS and IS stimulate significant cellular inflammation. Similar immune and cellular inflammatory responses were induced by PCS or IS on cultured proximal renal tubular cells.
KW - gene ontology
KW - indoxyl sulfate
KW - inflammation
KW - p-cresol sulfate
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U2 - 10.1093/ndt/gfs133
DO - 10.1093/ndt/gfs133
M3 - Article
C2 - 22610984
AN - SCOPUS:84872233428
SN - 0931-0509
VL - 28
SP - 70
EP - 78
JO - Nephrology Dialysis Transplantation
JF - Nephrology Dialysis Transplantation
IS - 1
ER -