Effects of the uremic toxin indoxyl sulphate on human microvascular endothelial cells.
HMEC-1 cells
cardiovascular diseases
chronic kidney disease
gel-free proteomic
indoxyl sulphate
Journal
Journal of applied toxicology : JAT
ISSN: 1099-1263
Titre abrégé: J Appl Toxicol
Pays: England
ID NLM: 8109495
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
revised:
14
07
2022
received:
08
06
2022
accepted:
15
07
2022
pubmed:
20
7
2022
medline:
15
11
2022
entrez:
19
7
2022
Statut:
ppublish
Résumé
Indoxyl sulphate (IS) is a uremic toxin accumulating in the plasma of chronic kidney disease (CKD) patients. IS accumulation induces side effects in the kidneys, bones and cardiovascular system. Most studies assessed IS effects on cell lines by testing higher concentrations than those measured in CKD patients. Differently, we exposed a human microvascular endothelial cell line (HMEC-1) to the IS concentrations measured in the plasma of healthy subjects (physiological) or CKD patients (pathological). Pathological concentrations reduced cell proliferation rate but did not increase long-term oxidative stress level. Indeed, total protein thiols decreased only after 24 h of exposure in parallel with an increased Nrf-2 protein expression. IS induced actin cytoskeleton rearrangement with formation of stress fibres. Proteomic analysis supported this hypothesis as many deregulated proteins are related to actin filaments organization or involved in the endothelial to mesenchymal transition. Interestingly, two proteins directly linked to cardiovascular diseases (CVD) in in vitro and in vivo studies underwent deregulation: COP9 signalosome complex subunit 9 and thrombomodulin. Future experiments will be needed to investigate the role of these proteins and the signalling pathways in which they are involved to clarify the possible link between CKD and CVD.
Identifiants
pubmed: 35854198
doi: 10.1002/jat.4366
pmc: PMC9796800
doi:
Substances chimiques
Indican
N187WK1Y1J
Uremic Toxins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1948-1961Subventions
Organisme : Università degli Studi di Milano
Informations de copyright
© 2022 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd.
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