IMR Press / FBL / Volume 23 / Issue 2 / DOI: 10.2741/4595

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article

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

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1 Centers for Metabolic Disease Research, Cardiovascular Research, & Thrombosis Research, Departments of Pharmacology, Lewis Katz School of Medicine at Temple University, USA
2 Division of Vascular Surgery, Department of Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USA
3 Shanxi Medical University, Taiyuan, 030001, China
4 The Shanxi Provincial People’s Hospital, an Affiliate Hospital of Shanxi Medical University, Taiyuan, Shanxi, 030001, China
5 Department of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China
Front. Biosci. (Landmark Ed) 2018, 23(2), 348–387; https://doi.org/10.2741/4595
Published: 1 January 2018
(This article belongs to the Special Issue Amylin in vasodilation, energy expenditure and inflammation)
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 1/80th 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.

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