Dataset Information

Protein Expression Profiling in Urinary Extracellular Vesicles Isolated from Patients with Chronic Kidney Disease and Renal Transplantation

ABSTRACT: The proposed project focuses on the study of urinary extracellular vesicles as a tool for the diagnosis and monitoring of kidney diseases, especially in patients undergoing kidney transplantation. We found a differential protein profile in patients with CKD before and after the transplant procedure.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Urine

DISEASE(S): Renal Failure

SUBMITTER: Emilie Pinault

LAB HEAD: Zesergio Carlo Melo Jerez

PROVIDER: PXD065380 | Pride | 2025-08-25

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	1F_RIPA_DIA_30x1_1ul_2054.d.zip	Other
	1F_RIPA_low-1.9sec_4ul_2040.tsv	Tabular
	1M_RIPA_DIA_30x1_1ul_2063.d.zip	Other
	1M_RIPA_low-1.9sec_4ul_2043.tsv	Tabular
	2F_RIPA_DIA_30x1_1ul_2061.d.zip	Other

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Publications

Potential kidney biomarkers in urinary extracellular vesicles from end stage renal disease and post-transplant patients.

Verdugo-Molinares Maritza G MG Ku-Centurion Marco M Cortes-Sanabria Laura L Lugo-Melchor Yadira O YO Pinault Emilie E Evangelista Luis L Ramos-Garcia Cesar O CO Marquet Pierre P Melo Zesergio Z

Journal of proteomics 20250818

Chronic kidney disease is a multifactorial entity characterized by decreased glomerular filtration rate (GFR). The last stage of the disease requires renal replacement therapy or kidney transplantation. As a disease with no treatment at earlier stages, and few biomarkers available, proteomics represent an excellent tool searching for new more efficient biomarkers. Urinary extracellular vesicles are an important source of information for kidney alterations, and their collection is not invasive. I ...[more]

PMID: 40834982

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Project description:Introduction: Altered metabolism is a key hallmark of tumour cells (Pavlova & Thompson, 2016) and has long been associated with relapse and resistance to treatment (Gonçalves et al., 2021; Lv et al., 2022). Recently, we identified a new role for histone deacetylase 6 (HDAC6) in the regulation of glycolytic metabolism (Dowling et al., 2021). HDAC6 is an atypical member of the HDAC family as it is localised in the cytosol, has two deacetylase domains, and contains a ubiquitin-binding domain (Gallinari et al., 2007). HDAC6 has been shown to deacetylate proteins involved in processes including microtubule remodelling and stress responses (Hubbert et al., 2002; Kawaguchi et al., 2003). In a recent publication, we showed that HDAC6 knockdown (K/D) or inhibition, with a compound we discovered called BAS-2, altered the acetylation of glycolytic enzymes and reduced glycolysis in triple-negative breast cancer (TNBC) cells (Dowling et al., 2021). However, we did not investigate whether HDAC6 inhibition altered other metabolic pathways at the time. The mitochondrial tricarboxylic acid (TCA) cycle plays an important role in tumour biology, not alone for energy production through the respiratory chain, but also for metabolic intermediates that serve as building blocks for lipid and nucleic acid synthesis (Eniafe & Jiang, 2021). Some of these intermediates of the TCA cycle have dual roles as ‘oncometabolites’ (Frezza, 2017). Both fumarate hydratase (FH) and succinate dehydrogenase (SDH), two key enzymes in the TCA cycle, are known tumour suppressors (Rustin et al., 2002; Schmidt et al., 2020). Loss of FH is associated with an aggressive form of kidney cancer called hereditary leiomyomatosis and renal cell carcinoma (HLRCC) (Tomlinson et al., 2002). Deficiency of FH causes an increase in fumarate, which has various signalling properties including the non-enzymatic formation of 2-(succino)cysteine (2-SC) adducts that can alter protein activity, a process termed succination (Guberovic & Frezza, 2024; Kinch et al., 2011; Tyrakis et al., 2017). Two recent publications identified that macrophages with FH deficiency show an increase of intracellular fumarate and that this alters mitochondrial structure, causing the release of mitochondrial DNA or RNA to activate inflammatory responses (Hooftman et al., 2023; Zecchini et al., 2023). To date, the majority of studies on FH have been carried out using knockout mice to show the role of FH in tumourigenesis or macrophage inflammation (Valcarcel-Jimenez & Frezza, 2023; Zecchini et al., 2023). However, there are limited studies in tumour cells on the role of FH or on how FH activity is regulated. In this study, we identified that HDAC6 can alter mitochondrial structure, causing cristae damage and the release of mtDNA into the cytosol. We then show by mass spectrometry, immunoprecipitation, and super-resolution imaging that HDAC6 and FH directly interact. Inhibition of HDAC6 with BAS-2 reduces FH activity, resulting in an increase of fumarate, with a downstream increase in protein succination. Utilising stochastic optical reconstruction microscopy (STORM), we pinpoint sites of interaction to the mitochondria, thereby demonstrating a novel regulation of FH in tumour cells.