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Open AccessArticle

Association between Circulation Indole-3-Acetic Acid Levels and Stem Cell Factor in Maintenance Hemodialysis Patients: A Cross-Sectional Study

by Ping-Hsun Wu 1,2,3,4, Yi-Ting Lin 1,2,4,5, Pei-Yu Wu 1,3,6, Hei-Hwa Lee 6, Su-Chu Lee 3, Szu-Chun Hung 7, Szu-Chia Chen 1,2,3,8, Mei-Chuan Kuo 2,3,9,* and Yi-Wen Chiu 2,3,9
1
Graduate Institute of Clinical Medicine, College of Medicines, Kaohsiung Medical University, Kaohsiung 807, Taiwan
2
Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
3
Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
4
Department of Medical Sciences, Uppsala University, Uppsala 75105, Sweden
5
Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
6
Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
7
Division of Nephrology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, and School of Medicine, Tzu Chi University, Hualien 23142, Taiwan
8
Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung 81267, Taiwan
9
Faculty of Renal Care, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2020, 9(1), 124; https://doi.org/10.3390/jcm9010124
Received: 1 December 2019 / Revised: 27 December 2019 / Accepted: 29 December 2019 / Published: 2 January 2020
(This article belongs to the Section Nephrology & Urology)
Protein-bound uremic toxin is a cardiovascular (CV) risk factor for patients with end-stage renal disease. Indole-3-acetic acid (IAA) was found to be associated with CV disease but the detailed pathophysiology remains unknown. Moreover, mitogen-activated protein kinase (MAPK) signaling cascades play an important role in the pathogenesis of CV disease. Thus, we explored the association between circulating IAA levels and forty MAPK cascade associated proteins in patients undergoing hemodialysis (HD). Circulating total form IAA was quantified by mass spectrometry and forty MAPK cascade associated proteins by a proximity extension assay in 331 prevalent HD patients. Accounting for multiple testing, and in multivariable-adjusted linear regression models, circulating total form IAA levels were positively associated with stem cell factor (β coefficient 0.13, 95% confidence interval 0.04 to 0.21, p = 0.004). A bioinformatics approach using the search tool for interactions of chemicals (STITCH) tool provided information that IAA may be involved in the regulation of cell proliferation, hematopoietic cells, and the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway. The knowledge gained here can be generalized, thereby impacting the non-traditional CV risk factors in patients with kidney disease. Further in vitro work is necessary to validate the translation of the mechanistic pathways. View Full-Text
Keywords: uremic toxins; indole-3-acetic acid; proteomics; mitogen-activated protein kinase cascade proteins; hemodialysis uremic toxins; indole-3-acetic acid; proteomics; mitogen-activated protein kinase cascade proteins; hemodialysis
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MDPI and ACS Style

Wu, P.-H.; Lin, Y.-T.; Wu, P.-Y.; Lee, H.-H.; Lee, S.-C.; Hung, S.-C.; Chen, S.-C.; Kuo, M.-C.; Chiu, Y.-W. Association between Circulation Indole-3-Acetic Acid Levels and Stem Cell Factor in Maintenance Hemodialysis Patients: A Cross-Sectional Study. J. Clin. Med. 2020, 9, 124.

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