Dataset Information

Urinary Glycosylated IGF2 peptides in association with CKD

ABSTRACT: Chronic kidney disease (CKD) is prevalent in 10% of world’s adult population, with Estimated Glomerular filtration rate (eGFR) and albuminuria employed in diagnosis. Role of protein glycosylation in causal mechanisms of CKD progression is largely unknown. Aim of this study was to identify urinary O-linked glycopeptides in association to CKD for better characterization of CKD molecular manifestations. Urine samples from 2 healthy and 8 CKD subjects were analyzed by CE-MS/MS and glycopeptide analysis using Proteome Discoverer 1.4. Distribution of identi-fied glycopeptides and correlation with Age, eGFR and Albuminuria were evaluated in 3810 da-tasets. In total, 17 O-linked glycopeptides from 7 different proteins were identified, derived primarily from Insulin-like growth factor-II (IGF2). Glycosylation occurred at the surface ex-posed IGF2 Threonine 96 position. Three glycopeptides (DVStPPTVLPDNFPRYPVGKF, DVStPPTVLPDNFPRYPVG and DVStPPTVLPDNFPRYP) exhibited positive correlation with Age. Glycopeptide (tPPTVLPDNFPRYP) showed strong negative association with eGFR. These results suggest that with aging and deteriorating kidney function, alterations in IGF2 proteoforms take place; which may reflect changes in mature IGF2 protein. Our results corroborate this hypothesis as IGF2 increased plasma levels were observed in CKD patients. Protease predictions, consider-ing also available transcriptomics data, suggest activation of cathepsin S with CKD, meriting further investigation.

INSTRUMENT(S): Thermo Finnigan instrument model

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Urine

DISEASE(S): Chronic Kidney Disease

SUBMITTER: Sonnal Lohia

LAB HEAD: Antonia Vlahou

PROVIDER: PXD039829 | Pride | 2023-05-10

REPOSITORIES: Pride

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Publications

Glycosylation Analysis of Urinary Peptidome Highlights IGF2 Glycopeptides in Association with CKD.

Lohia Sonnal S Latosinska Agnieszka A Zoidakis Jerome J Makridakis Manousos M Mischak Harald H Glorieux Griet G Vlahou Antonia A Jankowski Vera V

International journal of molecular sciences 20230311 6

Chronic kidney disease (CKD) is prevalent in 10% of world's adult population. The role of protein glycosylation in causal mechanisms of CKD progression is largely unknown. The aim of this study was to identify urinary O-linked glycopeptides in association to CKD for better characterization of CKD molecular manifestations. Urine samples from eight CKD and two healthy subjects were analyzed by CE-MS/MS and glycopeptides were identified by a specific software followed by manual inspection of the sp ...[more]

PMID: 36982475

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Project description:Cystinuria is the most frequent monogenic cause of renal calculi. We previously described a urinary inflammatory signature in 8 cystinuric patients through quantitative proteomic analysis. Our data suggested an association of abnormal renal function and an inflammatory protein profile. The objectives of the present study were to investigate: i) the urinary proteomic profile in cystinuric patients without chronic kidney disease (CKD), and in a control group of healthy volunteers; ii) the potential effect of urine alkalinization on the urinary proteomic profile in cystinuric patients as this is the cornerstone of the preventive medical treatment. Urinary inflammatory profile was evaluated at baseline in the control group and in cystinuric patients not yet treated or for whom the alkalizing treatment or the cysteine- binding thiols have been discontinuated for at least 3 months and with an eGFR (using the CKD-EPI formula) greater than 60 ml/min/1.73m2 (so without CKD G3-G5). In cystinuric patients, change from baseline urinary inflammatory profile was evaluated after 3 months of alkalizing treatment. Urine proteome was analyzed by Nano- liquid chromatography coupled to high resolution mass spectrometry. Twenty-one cystinuric patients (12 men, median age [IQR] 30.0 years [25.0 – 44.0]), and 7 healthy volunteers (2 men, median age 43.1 years [31.0 – 53.9]) were included. Median eGFR in these two groups was 95 ml/min/1.73m2 [87.5 – 111.5] and 116 ml/min/1.73m2 [91.0 – 120.0] respectively (p=0.38). Healthy volunteers had no inflammatory signature. The inflammatory signature was present in the cystinuric patients at different degrees. A hierarchical clustering of the cystinuric patients according to the intensity of the profile of core inflammation signature (11 proteins) was performed. The signature could clearly separate 5 cystinuric patients with a high inflammation from other cystinuric patients and healthy volunteers. The alkalizing treatment was associated with a decrease in the intensity of the urinary inflammatory profile in all 5 cystinuric patients compared to the initial high level of urinary inflammation. A panel of 11 proteins was found as elevated in some cystinuric patients without CKD G3- G5 and could work as an early inflammatory signature. The alkalizing treatment was associated with a reduction of this urinary inflammation signature, suggesting that this panel of proteins could also be a new tool to monitor the treatment of cystinuric patient.

			Action	DRS
	200415L000001.mgf	Mgf
	200415L000002.mgf	Mgf
	200415L000003.mgf	Mgf
	200415L000004.mgf	Mgf
	200424L000003.mgf	Mgf