Dataset Information

Proteomic analysis of endothelial cells and extracellular vesicles in response to indoxyl sulfate: mechanisms of endothelial dysfunction in chronic kidney disease

ABSTRACT: 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.

INSTRUMENT(S): Orbitrap Exploris 240

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Huvec Cell, Endothelial Cell

DISEASE(S): Chronic Kidney Disease

SUBMITTER: Fátima Santos

LAB HEAD: Matilde Alique

PROVIDER: PXD050628 | Pride | 2024-11-29

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20211126_12_1478_11_MV_IS2.pepXML	Pepxml
	20211126_12_1478_11_MV_IS2.raw	Raw
	20211126_12_1478_11_MV_IS2_uncalibrated.mgf	Mgf
	20211126_12_1478_5_Cells_IS2.raw	Raw
	20211126_12_1478_5_Cells_IS2_uncalibrated.mgf	Mgf

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Proteomic analysis of endothelial cells and extracellular vesicles in response to indoxyl sulfate: Mechanisms of endothelial dysfunction in chronic kidney disease.

Figuer Andrea A Santos Fátima M FM Ciordia Sergio S Valera Gemma G Martín-Jouve Beatriz B Hernández-Fonseca Juan Pablo JP Bodega Guillermo G Ceprián Noemí N Ramírez Rafael R Carracedo Julia J Alique Matilde M

Life sciences 20240611

<h4>Aims</h4>Cardiovascular pathology is the main cause of death in chronic kidney disease (CKD) patients. CKD is associated with the accumulation of uremic toxins in the bloodstream, and indoxyl sulfate (IS) is one of the most abundant uremic toxins found in the blood of CKD patients. We conducted an in vitro study to assess the mechanisms underlying the IS-induced endothelial dysfunction that could lead to cardiovascular diseases. We also studied their extracellular vesicles (EVs) owing to the ...[more]

PMID: 38871114

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