AUTHOR=Pang Shuting , Zhou Rongbin , Liu Zige , Xie Boji , Liu Fugang , Feng Bingmei , Chen Xuesong , Ruan Liangping , Chen Hong , Xie Yuli , Tan Qiuyan , Zhao Binran , Li Shanshan , Xue Chao , Yang Rirong , Li Wei 

TITLE=SPP1 as a biomarker for idiopathic membranous nephropathy progression and its regulatory role in inflammation and fibrosis

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1671891

DOI=10.3389/fimmu.2025.1671891

ISSN=1664-3224

ABSTRACT=ObjectiveIdiopathic membranous nephropathy (IMN) is a leading cause of nephrotic syndrome in middle-aged and elderly populations. Early intervention can delay disease progression and improve patient outcomes. This study aims to identify urinary biomarkers for IMN and investigate their association with disease progression, offering new insights for precise diagnosis and treatment.MethodsThis study began with RNA sequencing of three urine sample types (first-void morning urine, second-void morning urine, and random urine), combined with single-cell RNA sequencing of renal tissues. Bioinformatics analyses—including differential gene expression screening, machine learning, and molecular function annotation—were employed to identify potential IMN biomarkers. Furthermore, we established both a siRNA-mediated gene silencing model and a lentivirus transfection-mediated gene overexpression model in HK-2 cells. Subsequently, we investigated the functional mechanisms of the candidate biomarkers through qRT-PCR, Western blot, immunohistochemistry, and immunofluorescence assays.ResultsSPP1 was identified as a promising biomarker for IMN, demonstrating a critical role in promoting fibrosis and inflammatory responses associated with the disease. These findings suggest its potential as a novel therapeutic target for IMN intervention.