Uremic toxins are conditional danger- or homeostasis-associated molecular patterns

作者：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

来源：Frontiers in Bioscience-Landmark, 2018, 23(1): 348-387.

DOI：10.2741/4595

• Uremia
• Uremic Toxins
• Danger Signal-Associated Molecular Patterns
• Homeostasis-Associated Molecular Patterns
• DAMPs, HAMPs
• DAMP and HAMP receptors
• Inflammation

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/mflammatory cytokine pathways, rather than by purely passive accumulation.

• 出版日期2018-1-1
• 单位山西省人民医院; 山西医科大学; 南昌大学