PXD050628-1

PXD050628 is an original dataset announced via ProteomeXchange.

Title	Proteomic analysis of endothelial cells and extracellular vesicles in response to indoxyl sulfate: mechanisms of endothelial dysfunction in chronic kidney disease
Description	Introduction: Cardiovascular pathology is the main cause of death in patients with chronic kidney disease (CKD). CKD is associated with the accumulation of uremic toxins in the bloodstream due to their difficult elimination by renal substitution therapy. Indoxyl sulfate (IS) is one of the most abundant uremic toxins found in the blood of patients with CKD. We conducted an in vitro study to assess the mechanisms underlying IS-induced endothelial dysfunction that could lead to cardiovascular diseases. We studied not only endothelial cells but also their extracellular vesicles (EVs) owing to their capacity to act as messengers that transmit signals through their cargo. Methods: EVs were characterized using nanoparticle tracking analysis, transmission electron microscopy, and flow cytometry, and their tetraspanin expression was evaluated to confirm their identity as EVs. Subsequently, mass spectrophotometry of the protein lysates of cells and EVs was performed, followed by Gene Set Enrichment Analysis to identify the principal altered pathways. Additionally, qPCR and proliferation analyses were performed to confirm proteomic results. Results: Proteomic analysis of endothelial cells revealed that IS causes an increase in proteins related to adipogenesis, inflammation, and xenobiotic metabolism and a decrease in proliferation via mTOR. Inflammation due to TNF signaling via NFкB was confirmed by an increase in the expression of the target genes IL-6, MCP-1, and ICAM-1. Concerning EVs, extracellular matrix elements were reduced, and myogenesis genes were downregulated in response to UV irradiation and inflammation. Fatty acid metabolism also seemingly increases, which, along with adipogenesis and inflammation observed in cells, could be related to atherosclerosis. Conclusions: Endothelial cells treated with IS had more proteins related to adipogenesis, inflammation, and xenobiotic metabolism and fewer associated with proliferation. Furthermore, EVs from cells treated with IS may mediate endothelial dysfunction, since they present fewer extracellular matrix elements, myogenesis and inflammatory factors, and proteins downregulated in response to UV radiation.
HostingRepository	PRIDE
AnnounceDate	2024-11-29
AnnouncementXML	Submission_2024-11-29_05:42:19.664.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD050628
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Fátima Santos
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 240

Revision	Datetime	Status	ChangeLog Entry
0	2024-03-14 15:59:25	ID requested
⏵ 1	2024-11-29 05:42:20	announced

Figuer A, Santos FM, Ciordia S, Valera G, Mart, í, n-Jouve B, Hern, á, ndez-Fonseca JP, Bodega G, Cepri, á, n N, Ram, í, rez R, Carracedo J, Alique M, Proteomic analysis of endothelial cells and extracellular vesicles in response to indoxyl sulfate: Mechanisms of endothelial dysfunction in chronic kidney disease. Life Sci, 351():122810(2024) [pubmed]

10.6019/PXD050628;

10.1016/j.lfs.2024.122810;

submitter keyword: cardiovascular disease, chronic kidney disease, indoxyl sulfate, proteomics, endothelial dysfunction, extracellular vesicles

Matilde Alique
contact affiliation	Departamento de Biología de Sistemas, Universidad de Alcalá, 28871 Alcala de Henares, Madrid, Spain
contact email	matilde.alique@uah.es
lab head
Fátima Santos
contact affiliation	CNB
contact email	ftxsantos@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD050628
     1. Label: PRIDE project
     2. Name: Proteomic analysis of endothelial cells and extracellular vesicles in response to indoxyl sulfate: mechanisms of endothelial dysfunction in chronic kidney disease