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Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Front+Biosci+(Landmark+Ed) 2018 ; 23 (ä): 348-87 Nephropedia Template TP
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Uremic toxins are conditional danger- or homeostasis-associated molecular patterns #MMPMID28930551
Sun Y; Johnson C; Zhou J; Wang L; Li YF; Lu Y; Nanayakkara G; Fu H; Shao Y; Sanchez C; Yang WY; Wang X; Choi ET; Li R; Wang H; Yang XF
Front Biosci (Landmark Ed) 2018[Jan]; 23 (ä): 348-87 PMID28930551show ga
We mined novel uremic toxin (UT) metabolomics/gene databases, and analyzed the expression changes of UT receptors and UT synthases in chronic kidney disease (CKD) and cardiovascular disease (CVD). We made the following observations: 1) UTs represent only 1/80th of human serum small-molecule metabolome; 2) Some UTs are increased in CKD and CVD; 3) UTs either induce or suppress the expression of inflammatory molecules; 4) The expression of UT genes is significantly modulated in CKD patients, and coronary artery disease (CAD) patients; 5) The expression of UT genes is upregulated by caspase-1 and TNF-alpha pathways but is inhibited in regulatory T cells. These results demonstrate that UTs are selectively increased, and serve as danger signal-associated molecular patterns (DAMPs) and homeostasis-associated molecular patterns (HAMPs) that modulate inflammation. These results also show that some UT genes are upregulated in CKD and CAD via caspase-1/inflammatory cytokine pathways, rather than by purely passive accumulation.