PMID- 37511514 OWN - NLM STAT- MEDLINE DCOM- 20230731 LR - 20230801 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 24 IP - 14 DP - 2023 Jul 21 TI - Towards the Definition of the Molecular Hallmarks of Idiopathic Membranous Nephropathy in Serum Proteome: A DIA-PASEF Approach. LID - 10.3390/ijms241411756 [doi] LID - 11756 AB - Idiopathic membranous nephropathy (IMN) is a pathologically defined disorder of the glomerulus, primarily responsible for nephrotic syndromes (NS) in nondiabetic adults. The underlying molecular mechanisms are still not completely clarified. To explore possible molecular and functional signatures, an optimised mass spectrometry (MS) method based on next-generation data-independent acquisition combined with ion-mobility was applied to serum of patients affected by IMN (n = 15) or by other glomerulopathies (PN) (n = 15). The statistical comparison highlighted a panel of 57 de-regulated proteins with a significant increase in lipoprotein-related proteins (APOC1, APOB, APOA1, APOL1 and LCAT) and a substantial quantitative alteration of key serpins (including A4, D1, A7, A6, F2, F1 and 1) possibly associated with IMN or NS and podocyte stress. A critical dysregulation in metabolisms of lipids (e.g., VLDL assembly and clearance) likely to be related to known hyperlipidemia in IMN, along with involvement of non-classical complement pathways and a putative enrolment of ficolin-2 in sustaining the activation of the lectin-mediated complement system have been pinpointed. Moreover, mannose receptor CD206 (MRC1-down in IMN) and biotinidase (BTD-up in IMN) are able alone to accurately distinguish IMN vs. PN. To conclude, our work provides key proteomic insights into the IMN complexity, opening the way to an efficient stratification of MN patients. FAU - Previtali, Paolo AU - Previtali P AUID- ORCID: 0000-0001-7837-0798 AD - Proteomics and Metabolomics Unit, School of Medicine and Surgery, University of Milano-Bicocca, 20854 Vedano al Lambro, Italy. FAU - Pagani, Lisa AU - Pagani L AUID- ORCID: 0000-0002-9870-932X AD - Proteomics and Metabolomics Unit, School of Medicine and Surgery, University of Milano-Bicocca, 20854 Vedano al Lambro, Italy. FAU - Risca, Giulia AU - Risca G AUID- ORCID: 0000-0002-6389-9434 AD - Bicocca Bioinformatics Biostatistics and Bioimaging Centre-B4, School of Medicine and Surgery, University of Milano-Bicocca, 20854 Vedano al Lambro, Italy. FAU - Capitoli, Giulia AU - Capitoli G AUID- ORCID: 0000-0002-8178-2440 AD - Bicocca Bioinformatics Biostatistics and Bioimaging Centre-B4, School of Medicine and Surgery, University of Milano-Bicocca, 20854 Vedano al Lambro, Italy. FAU - Bossi, Eleonora AU - Bossi E AD - Proteomics and Metabolomics Unit, School of Medicine and Surgery, University of Milano-Bicocca, 20854 Vedano al Lambro, Italy. FAU - Oliveira, Glenda AU - Oliveira G AD - Proteomics and Metabolomics Unit, School of Medicine and Surgery, University of Milano-Bicocca, 20854 Vedano al Lambro, Italy. FAU - Piga, Isabella AU - Piga I AUID- ORCID: 0000-0001-8221-2493 AD - Proteomics and Metabolomics Unit, School of Medicine and Surgery, University of Milano-Bicocca, 20854 Vedano al Lambro, Italy. FAU - Radice, Antonella AU - Radice A AD - Microbiology Institute, ASST (Azienda Socio Sanitaria Territoriale) Santi Paolo e Carlo, 20142 Milan, Italy. FAU - Trezzi, Barbara AU - Trezzi B AD - Department of Medicine and Surgery, University of Milano Bicocca and Nephrology, 20900 Monza, Italy. AD - Dialysis Unit, ASST-Monza, Ospedale San Gerardo, 20900 Monza, Italy. FAU - Sinico, Renato Alberto AU - Sinico RA AUID- ORCID: 0000-0002-9470-218X AD - Department of Medicine and Surgery, University of Milano Bicocca and Nephrology, 20900 Monza, Italy. AD - Dialysis Unit, ASST-Monza, Ospedale San Gerardo, 20900 Monza, Italy. FAU - Magni, Fulvio AU - Magni F AUID- ORCID: 0000-0002-8663-0374 AD - Proteomics and Metabolomics Unit, School of Medicine and Surgery, University of Milano-Bicocca, 20854 Vedano al Lambro, Italy. FAU - Chinello, Clizia AU - Chinello C AUID- ORCID: 0000-0002-7921-7768 AD - Proteomics and Metabolomics Unit, School of Medicine and Surgery, University of Milano-Bicocca, 20854 Vedano al Lambro, Italy. LA - eng GR - FAR 2017-2021/Fondo Ateneo-UNIMIB/ GR - Fondazione Gigi & Pupa Ferrari Onlus/Fondazione Gigi & Pupa Ferrari Onlus/ GR - regional law n degrees 9/2020, resolution n degrees 3776/2020": PROGRAMMA DEGLI INTERVENTI PER LA RIPRESA ECONOMICA: SVILUPPO DI NUOVI ACCORDI DI COLLABORAZIONE CON LE UNIVERSITA PER LA RICERCA, L'INNOVAZIONE E IL TRASFERIMENTO TECNOLOGICO: NephropaThy/Regione Lombardia/ PT - Journal Article DEP - 20230721 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Proteome) RN - 0 (APOL1 protein, human) RN - 0 (Apolipoprotein L1) SB - IM MH - Adult MH - Humans MH - *Glomerulonephritis, Membranous MH - Proteome MH - Proteomics MH - Kidney Glomerulus/metabolism MH - *Nephrotic Syndrome MH - Apolipoprotein L1 PMC - PMC10380405 OTO - NOTNLM OT - DIA-PASEF OT - mass spectrometry OT - membranous nephropathies OT - proteomics OT - serum COIS- The authors declare no conflict of interest. EDAT- 2023/07/29 11:44 MHDA- 2023/07/31 06:43 PMCR- 2023/07/21 CRDT- 2023/07/29 01:24 PHST- 2023/05/25 00:00 [received] PHST- 2023/06/30 00:00 [revised] PHST- 2023/07/17 00:00 [accepted] PHST- 2023/07/31 06:43 [medline] PHST- 2023/07/29 11:44 [pubmed] PHST- 2023/07/29 01:24 [entrez] PHST- 2023/07/21 00:00 [pmc-release] AID - ijms241411756 [pii] AID - ijms-24-11756 [pii] AID - 10.3390/ijms241411756 [doi] PST - epublish SO - Int J Mol Sci. 2023 Jul 21;24(14):11756. doi: 10.3390/ijms241411756.