Indoxyl sulfate-mediated metabolic alteration of transcriptome signatures in monocytes of patients with end-stage renal disease (ESRD)

Hee Young Kim, Su Jeong Lee, Yuri Hwang, Ga Hye Lee, Chae Eun Yoon, Hyeon Chang Kim, Tae Hyun Yoo, Won Woo Lee

Research output: Contribution to journalArticlepeer-review

Abstract

End-stage renal disease (ESRD) is the final stage of chronic kidney disease, which is increasingly prevalent worldwide and is associated with the progression of cardiovascular disease (CVD). Indoxyl sulfate (IS), a major uremic toxin, plays a key role in the pathology of CVD via adverse effects in endothelial and immune cells. Thus, there is a need for a transcriptomic overview of IS responsive genes in immune cells of ESRD patients. Here, we investigated IS-mediated alterations in gene expression in monocytes from ESRD patients. Transcriptomic analysis of ESRD patient-derived monocytes and IS-stimulated monocytes from healthy controls was performed, followed by analysis of differentially expressed genes (DEGs) and gene ontology (GO). We found that 148 upregulated and 139 downregulated genes were shared between ESRD patient-derived and IS-stimulated monocytes. Interaction network analysis using STRING and ClueGo suggests that mainly metabolic pathways, such as the pentose phosphate pathway, are modified by IS in ESRD patient-derived monocytes. These findings were confirmed in IS-stimulated monocytes by the increased mRNA expression of genes including G6PD, PGD, and TALDO1. Our data suggest that IS causes alteration of metabolic pathways in monocytes of ESRD patients and, thus, these altered genes may be therapeutic targets.

Original languageEnglish
Article numberA12
JournalToxins
Volume12
Issue number10
DOIs
Publication statusPublished - 2020 Oct

Bibliographical note

Funding Information:
Funding: This work was supported in part by a grant (HI13C0715 to W.-W.L.) from the Korean Health Technology Research and Development Project (Ministry of Health and Welfare, Sejong City, South Korea) and by grants (Grant no: NRF-2018R1A2B2006310 to W.W. Lee, NRF-2019R1H1A2101272 and NRF-2020R1I1A1A01063010 to H.Y.K) from the National Research Foundation of Korea (NRF) funded by Ministry of Science and ICT (MSIT), Republic of Korea, and by a grant (No. 0320200260: 2020-1725 to W-W. Lee) from the Seoul National University Hospital (SNUH) Research Fund.

Funding Information:
This work was supported in part by a grant (HI13C0715 to W.-W.L.) from the Korean Health Technology Research and Development Project (Ministry of Health and Welfare, Sejong City, South Korea) and by grants (Grant no: NRF-2018R1A2B2006310 to W.W. Lee, NRF-2019R1H1A2101272 and NRF-2020R1I1A1A01063010 to H.Y.K) from the National Research Foundation of Korea (NRF) funded by Ministry of Science and ICT (MSIT), Republic of Korea, and by a grant (No. 0320200260: 2020-1725 to W-W. Lee) from the Seoul National University Hospital (SNUH) Research Fund. The authors thank Jiyeon Jang (Seoul National University College of Medicine) for assisting in the recruitment of human subjects and thank Core Lab, Clinical Trials Center, Seoul National University Hospital for drawing blood.

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Health, Toxicology and Mutagenesis

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