Maslyennikov Yuriy, Pralea Ioana-Ecaterina, Bărar Andrada Alina, Rusu Crina Claudia, Moldovan Diana Tania, Potra Alina Ramona, Tirinescu Dacian, Țicală Maria, Urs Alexandra, Zamfir Paula, Boțan Emil, Mureșan Ximena-Maria, Pîrv Simina, Nuțu Andreea, Berindan-Neagoe Ioana, Iuga Cristina-Adela, Kacso Ina Maria
Department of Nephrology, Faculty of Medicine, "Iuliu Hațieganu" University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania.
Personalized Medicine and Rare Diseases Department, MEDFUTURE-Institute for Biomedical Research, "Iuliu Hațieganu" University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania.
Life (Basel). 2025 Mar 23;15(4):527. doi: 10.3390/life15040527.
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 ( < 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.
足细胞损伤是局灶节段性肾小球硬化（FSGS）和微小病变病（MCD）的共同特征，最终表现为足突消失和蛋白尿。然而，导致足细胞细胞骨架重排的触发因素和致病途径尚未完全阐明。在此，我们旨在通过对MCD和FSGS患者激光捕获显微切割肾小球进行组织自下而上的蛋白质组分析，来增进对这些途径的理解。两组之间共鉴定出46种差异表达蛋白（<0.05，|FC|≥1.2）。通路分析表明，46种蛋白中有16种与免疫系统相关，其中E2泛素结合酶（UBE2K）和补体因子H相关蛋白1（CFHR1）在FSGS中与MCD相比具有最高的倍数变化。通过免疫组织化学进一步验证了这两种靶蛋白，证实了UBE2K在足细胞中的定位以及CFHR在内皮细胞中的染色。此外，其他几种差异表达蛋白与细胞骨架结构及其调节有关。我们的结果表明，补体失调可能是FSGS中细胞骨架重排的根源。
