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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
Uremic toxins are conditional danger- or homeostasis-associated molecular patterns
Front Biosci (Landmark Ed). 2018 Jan 1;23 :348-387
PMID: 28930551    PMCID: PMC5627515   
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Abstract
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 1/80(th) 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.
Notes
1093-4715 Sun, Yu Johnson, Candice Zhou, Jun Wang, Luqiao Li, Ya-Feng Lu, Yifan Nanayakkara, Gayani Fu, Hangfei Shao, Ying Sanchez, Claudette Yang, William Y Wang, Xin Choi, Eric T Li, Rongshan Wang, Hong Yang, Xiao-Feng R01 DK113775/DK/NIDDK NIH HHS/United States R01 HL130233/HL/NHLBI NIH HHS/United States R01 HL131460/HL/NHLBI NIH HHS/United States R01 DK104116/DK/NIDDK NIH HHS/United States R01 HL132399/HL/NHLBI NIH HHS/United States Journal Article United States Front Biosci (Landmark Ed). 2018 Jan 1;23:348-387.