Pathogenesis of Focal Segmental Glomerulosclerosis and Minimal Change Disease: Insights from Glomerular Proteomics
Podocyte injury is a hallmark of both focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD), ultimately reflected in foot process effacement and proteinuria. Triggers and pathogenic pathways leading to podocyte cytoskeleton rearrangements are, however, incompletely explained. He...
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2025-03-01
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| author | Yuriy Maslyennikov Ioana-Ecaterina Pralea Andrada Alina Bărar Crina Claudia Rusu Diana Tania Moldovan Alina Ramona Potra Dacian Tirinescu Maria Țicală Alexandra Urs Paula Zamfir Emil Boțan Ximena-Maria Mureșan Simina Pîrv Andreea Nuțu Ioana Berindan-Neagoe Cristina-Adela Iuga Ina Maria Kacso |
| author_facet | Yuriy Maslyennikov Ioana-Ecaterina Pralea Andrada Alina Bărar Crina Claudia Rusu Diana Tania Moldovan Alina Ramona Potra Dacian Tirinescu Maria Țicală Alexandra Urs Paula Zamfir Emil Boțan Ximena-Maria Mureșan Simina Pîrv Andreea Nuțu Ioana Berindan-Neagoe Cristina-Adela Iuga Ina Maria Kacso |
| author_sort | Yuriy Maslyennikov |
| collection | DOAJ |
| description | Podocyte injury is a hallmark of both focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD), ultimately reflected in foot process effacement and proteinuria. Triggers and pathogenic pathways leading to podocyte cytoskeleton rearrangements are, however, incompletely explained. Here, we aimed to contribute to the understanding of these pathways using tissue bottom-up proteomic profiling of laser-capture microdissected glomeruli from MCD and FSGS. Forty-six differentially expressed proteins were identified between the two groups (<i>p</i> < 0.05, |FC| ≥ 1.2). Pathway analysis showed that 16 out of 46 proteins were associated with the immune system, with E2 ubiquitin-conjugating enzyme (UBE2K) and complement factor H-related protein-1 (CFHR1) yielding the highest fold change in FSGS compared to MCD. The two target proteins were further validated through immunohistochemistry, confirming the podocyte localization of UBE2K and endothelial staining of CFHR. Additionally, several other differentially expressed proteins were linked to the cytoskeleton structure and its regulation. Our results point to the possibility that complement dysregulation may be the source of cytoskeleton rearrangement in FSGS. |
| format | Article |
| id | doaj-art-cb194bffb06b4d8bb02f714e98dedb0c |
| institution | OA Journals |
| issn | 2075-1729 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
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| series | Life |
| spelling | doaj-art-cb194bffb06b4d8bb02f714e98dedb0c2025-08-20T02:28:32ZengMDPI AGLife2075-17292025-03-0115452710.3390/life15040527Pathogenesis of Focal Segmental Glomerulosclerosis and Minimal Change Disease: Insights from Glomerular ProteomicsYuriy Maslyennikov0Ioana-Ecaterina Pralea1Andrada Alina Bărar2Crina Claudia Rusu3Diana Tania Moldovan4Alina Ramona Potra5Dacian Tirinescu6Maria Țicală7Alexandra Urs8Paula Zamfir9Emil Boțan10Ximena-Maria Mureșan11Simina Pîrv12Andreea Nuțu13Ioana Berindan-Neagoe14Cristina-Adela Iuga15Ina Maria Kacso16Department of Nephrology, Faculty of Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, RomaniaPersonalized Medicine and Rare Diseases Department, MEDFUTURE—Institute for Biomedical Research, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, RomaniaDepartment of Nephrology, Faculty of Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, RomaniaDepartment of Nephrology, Faculty of Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, RomaniaDepartment of Nephrology, Faculty of Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, RomaniaDepartment of Nephrology, Faculty of Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, RomaniaDepartment of Nephrology, Faculty of Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, RomaniaDepartment of Nephrology, Faculty of Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, RomaniaDepartment of Nephrology, Faculty of Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, RomaniaDepartment of Pathology, Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, RomaniaDepartment of Pathology, County Emergency Hospital Cluj-Napoca, 400347 Cluj-Napoca, RomaniaPersonalized Medicine and Rare Diseases Department, MEDFUTURE—Institute for Biomedical Research, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, RomaniaPersonalized Medicine and Rare Diseases Department, MEDFUTURE—Institute for Biomedical Research, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, RomaniaGenomics Department, Institute for Biomedical Research, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, RomaniaGenomics Department, Institute for Biomedical Research, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, RomaniaPersonalized Medicine and Rare Diseases Department, MEDFUTURE—Institute for Biomedical Research, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, RomaniaDepartment of Nephrology, Faculty of Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, RomaniaPodocyte injury is a hallmark of both focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD), ultimately reflected in foot process effacement and proteinuria. Triggers and pathogenic pathways leading to podocyte cytoskeleton rearrangements are, however, incompletely explained. Here, we aimed to contribute to the understanding of these pathways using tissue bottom-up proteomic profiling of laser-capture microdissected glomeruli from MCD and FSGS. Forty-six differentially expressed proteins were identified between the two groups (<i>p</i> < 0.05, |FC| ≥ 1.2). Pathway analysis showed that 16 out of 46 proteins were associated with the immune system, with E2 ubiquitin-conjugating enzyme (UBE2K) and complement factor H-related protein-1 (CFHR1) yielding the highest fold change in FSGS compared to MCD. The two target proteins were further validated through immunohistochemistry, confirming the podocyte localization of UBE2K and endothelial staining of CFHR. Additionally, several other differentially expressed proteins were linked to the cytoskeleton structure and its regulation. Our results point to the possibility that complement dysregulation may be the source of cytoskeleton rearrangement in FSGS.https://www.mdpi.com/2075-1729/15/4/527focal segmental glomerulosclerosisminimal change diseaseproteomicstissueglomeruli |
| spellingShingle | Yuriy Maslyennikov Ioana-Ecaterina Pralea Andrada Alina Bărar Crina Claudia Rusu Diana Tania Moldovan Alina Ramona Potra Dacian Tirinescu Maria Țicală Alexandra Urs Paula Zamfir Emil Boțan Ximena-Maria Mureșan Simina Pîrv Andreea Nuțu Ioana Berindan-Neagoe Cristina-Adela Iuga Ina Maria Kacso Pathogenesis of Focal Segmental Glomerulosclerosis and Minimal Change Disease: Insights from Glomerular Proteomics Life focal segmental glomerulosclerosis minimal change disease proteomics tissue glomeruli |
| title | Pathogenesis of Focal Segmental Glomerulosclerosis and Minimal Change Disease: Insights from Glomerular Proteomics |
| title_full | Pathogenesis of Focal Segmental Glomerulosclerosis and Minimal Change Disease: Insights from Glomerular Proteomics |
| title_fullStr | Pathogenesis of Focal Segmental Glomerulosclerosis and Minimal Change Disease: Insights from Glomerular Proteomics |
| title_full_unstemmed | Pathogenesis of Focal Segmental Glomerulosclerosis and Minimal Change Disease: Insights from Glomerular Proteomics |
| title_short | Pathogenesis of Focal Segmental Glomerulosclerosis and Minimal Change Disease: Insights from Glomerular Proteomics |
| title_sort | pathogenesis of focal segmental glomerulosclerosis and minimal change disease insights from glomerular proteomics |
| topic | focal segmental glomerulosclerosis minimal change disease proteomics tissue glomeruli |
| url | https://www.mdpi.com/2075-1729/15/4/527 |
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