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ORIGINAL RESEARCH article

Front. Immunol.

Sec. Inflammation

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1671891

SPP1 as a Biomarker for Idiopathic Membranous Nephropathy Progression and Its Regulatory Role in Inflammation and Fibrosis

Provisionally accepted
Wei  LiWei Li1*Shuting  PangShuting Pang1Rongbin  ZhouRongbin Zhou2Zige  LiuZige Liu2Boji  XieBoji Xie1Fugang  LiuFugang Liu1Bingmei  FengBingmei Feng1Xuesong  ChenXuesong Chen1Liangping  RuanLiangping Ruan1Hong  ChenHong Chen1Yuli  XieYuli Xie2Qiuyan  TanQiuyan Tan1Binran  ZhaoBinran Zhao1Shanshan  LiShanshan Li1Chao  XueChao Xue1RIRONG  YANGRIRONG YANG2
  • 1Second Affiliated Hospital of Guangxi Medical University, Nanning, China
  • 2Guangxi Medical University, Nanning, China

The final, formatted version of the article will be published soon.

Objective Idiopathic 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. Methods This 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. Results SPP1 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.

Keywords: Idiopathic membranous nephropathy, Proximal tubular cells, SPP1, Fibrosis, Inflammation

Received: 23 Jul 2025; Accepted: 08 Sep 2025.

Copyright: © 2025 Li, Pang, Zhou, Liu, Xie, Liu, Feng, Chen, Ruan, Chen, Xie, Tan, Zhao, Li, Xue and YANG. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Wei Li, Second Affiliated Hospital of Guangxi Medical University, Nanning, China

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