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

Yu Sun; Candice Johnson; Jun Zhou; Luqiao Wang; Ya Feng Li; Yifan Lu; Gayani Nanayakkara; Hangfei Fu; Ying Shao; Claudette Sanchez; William Y. Yang; Xin Wang; Eric T. Choi; Rongshan Li; Hong Wang; Xiao Feng Yang

doi:10.2741/4595

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

Yu Sun, Candice Johnson, Jun Zhou, Luqiao Wang, Ya Feng Li, Yifan Lu, Gayani Nanayakkara, Hangfei Fu, Ying Shao, Claudette Sanchez, William Y. Yang, Xin Wang, Eric T. Choi, Rongshan Li, Hong Wang, Xiao Feng Yang

Research output: Contribution to journal › Article › peer-review

34 Scopus citations

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.

Original language	English
Pages (from-to)	348-387
Number of pages	40
Journal	Frontiers in Bioscience - Landmark
Volume	23
Issue number	2
DOIs	https://doi.org/10.2741/4595
State	Published - Jan 1 2018
Externally published	Yes

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.2741/4595

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title = "Uremic toxins are conditional danger- or homeostasis-associated molecular patterns",

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

author = "Yu Sun and Candice Johnson and Jun Zhou and Luqiao Wang and Li, {Ya Feng} and Yifan Lu and Gayani Nanayakkara and Hangfei Fu and Ying Shao and Claudette Sanchez and Yang, {William Y.} and Xin Wang and Choi, {Eric T.} and Rongshan Li and Hong Wang and Yang, {Xiao Feng}",

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doi = "10.2741/4595",

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TY - JOUR

T1 - Uremic toxins are conditional danger- or homeostasis-associated molecular patterns

AU - Sun, Yu

AU - Johnson, Candice

AU - Zhou, Jun

AU - Wang, Luqiao

AU - Li, Ya Feng

AU - Lu, Yifan

AU - Nanayakkara, Gayani

AU - Fu, Hangfei

AU - Shao, Ying

AU - Sanchez, Claudette

AU - Yang, William Y.

AU - Wang, Xin

AU - Choi, Eric T.

AU - Li, Rongshan

AU - Wang, Hong

AU - Yang, Xiao Feng

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

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KW - DAMPs

KW - Danger Signal-Associated Molecular Patterns

KW - HAMP receptors

KW - HAMPs

KW - Homeostasis-Associated Molecular Patterns

KW - Inflammation

KW - Uremia

KW - Uremic Toxins

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

Abstract

Keywords

UN SDGs

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