Dataset Information

Comparative proteomic analysis of microvescicoles and exosomes isolated from urine of medullary sponge kidney disease (MSK) versus Autosomal dominant polycystic kidney disease (ADPKD) patients.

ABSTRACT: Microvescicles (MV) and exosomes (EX) seem to be involved in the pathogenetic machinery of the autosomal dominant polycystic kidney disease (ADPKD), but, at the moment, no studies have assessed their role in medullary sponge kidney disease (MSK), a sporadic kidney malformation featuring cysts, nephrocalcinosis and recurrent renal stones. To discover their role in this disease we employed a proteomic-based research strategy.

INSTRUMENT(S): Orbitrap Fusion ETD

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Andrea Petretto

LAB HEAD: Andrea Petretto

PROVIDER: PXD011283 | Pride | 2019-11-25

REPOSITORIES: pride

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Source:

			Action	DRS
	Bruschi.zip	Other
	Candiano_F_1017_ESO_urine_MSK_10_068.raw	Raw
	Candiano_F_1017_ESO_urine_MSK_1_061.raw	Raw
	Candiano_F_1017_ESO_urine_MSK_2_062.raw	Raw
	Candiano_F_1017_ESO_urine_MSK_31_069.raw	Raw

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Project description:Peritoneal dialysis (PD) is the worldwide recognized preferred dialysis treatment for children affected by end-stage kidney disease (ESKD). However, due to the unphysiological composition of PD fluids, the peritoneal membrane (PM) of these patients may undergo structural and functional alterations, which may cause fibrosis. Several factors may accelerate this process and primary kidney disease may have a causative role. In particular, patients affected by corticoresistant primary focal segmental glomerulosclerosis), a rare glomerular disease leading to nephrotic syndrome and ESKD, seem more prone to develop peritoneal fibrosis. The mechanism causing this predisposition is still unrecognized. To better define this condition, we carried out, for the first time, a new comprehensive comparative proteomic mass spectrometry analysis of mesothelial exosomes from peritoneal dialysis effluent (PDE) of 6 pediatric patients with focal segmental glomerular sclerosis (FSGS) versus 6 patients affected by other primary renal diseases (No FSGS). Our omic study demonstrated that, despite the high overlap in the protein milieu between the two study groups, machine learning allowed a complete distinction of the whole proteomic exosome mesothelial content of FSGS versus No FSGS (with 100% accuracy). Out of the 2490 identified proteins, 40% (995) were involved in epithelial-mesenchymal transition (EMT)/fibrosis and in the transforming growth factor-β pathway. Additionally, the Weight Gene Co-expression Network Analysis algorithm identified that some of the discriminative proteins (TIMP1, CTHRC1, SPARC, CHMP4B, COL5A2, ANXA13, FNC2 and CENP-E) were also highly correlated to PD vintage, fibrosis, EMT and non-neoplastic PM disease. All together our data demonstrated that mesothelial cells of FSGS patients are more prone to activate a pro-fibrotic machinery with exosomes having a primary role in this process. Moreover, they indicated that identified FSGS-associated elements in mesothelial exosome protein could be employed as potential new biomarkers of mesothelial integrity. Finally, our results highlighted that in FSGS patients particular attention should be paid to use more biocompatible dialysis solution, reduce the length of time on PD and personalize PD regimens to minimize the risk of rapid loss of PM function or development of encapsulating peritoneal sclerosis.

Dataset Information

Comparative proteomic analysis of microvescicoles and exosomes isolated from urine of medullary sponge kidney disease (MSK) versus Autosomal dominant polycystic kidney disease (ADPKD) patients.

Dataset's files

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