Scholarlink

<p>Randall’s plaque (RP) formation is a critical initiating process in calcium oxalate nephrolithiasis; however, the molecular mechanisms driving its pathogenesis remain incompletely understood. This study aimed to evaluate the role of fatty acid-binding protein 3 (FABP3), a key regulator of lipid metabolism and epithelial homeostasis, in RP development. We employed an integrative multi-omics approach incorporating single-cell RNA sequencing (scRNA-seq), quantitative real-time PCR (qPCR), immunohistochemistry (IHC), and pathway enrichment analyses on human renal papillary tissues from individuals with and without RP, alongside validation in a murine model. scRNA-seq revealed significant downregulation of FABP3 across 21 renal cell clusters within the RP microenvironment (mean expression: 0.0188). qPCR confirmed a tenfold reduction in FABP3 transcript levels in RP samples compared to controls (2^-ΔCt: 0.0714 vs. 0.6998; Cp values 24.05–25.31 vs. 20.97–22.77; <i>p</i> &lt; 0.001), while IHC demonstrated parallel protein depletion in murine RP tissues. Functional enrichment analyses linked FABP3 deficiency to dysregulation of lipid metabolic pathways, including fatty acid transport and lipolysis, implicating these alterations in interstitial calcium deposition and plaque formation. In conclusion, this study identifies FABP3 as a central molecular determinant in RP pathogenesis, offering novel mechanistic insight and establishing FABP3 as a promising biomarker and therapeutic target for nephrolithiasis prevention.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

FABP3 deficiency exacerbates renal Randall plaque formation: insights from single-cell RNA transcriptomic analysis

  • 期刊论文

  • 发表日期：

    2025年12月1日

查看全文
  • Muhammad Sarfaraz Iqbal,
  • Xiaolu Duan,
  • Kotb A. Attia,
  • Ghulam Nabi,
  • Kaoqing Peng,
  • Nimra Sardar,
  • Di Gu,
  • Guohua Zeng,
  • Nada S. Al-Theyab

摘要

Randall’s plaque (RP) formation is a critical initiating process in calcium oxalate nephrolithiasis; however, the molecular mechanisms driving its pathogenesis remain incompletely understood. This study aimed to evaluate the role of fatty acid-binding protein 3 (FABP3), a key regulator of lipid metabolism and epithelial homeostasis, in RP development. We employed an integrative multi-omics approach incorporating single-cell RNA sequencing (scRNA-seq), quantitative real-time PCR (qPCR), immunohistochemistry (IHC), and pathway enrichment analyses on human renal papillary tissues from individuals with and without RP, alongside validation in a murine model. scRNA-seq revealed significant downregulation of FABP3 across 21 renal cell clusters within the RP microenvironment (mean expression: 0.0188). qPCR confirmed a tenfold reduction in FABP3 transcript levels in RP samples compared to controls (2^-ΔCt: 0.0714 vs. 0.6998; Cp values 24.05–25.31 vs. 20.97–22.77; p < 0.001), while IHC demonstrated parallel protein depletion in murine RP tissues. Functional enrichment analyses linked FABP3 deficiency to dysregulation of lipid metabolic pathways, including fatty acid transport and lipolysis, implicating these alterations in interstitial calcium deposition and plaque formation. In conclusion, this study identifies FABP3 as a central molecular determinant in RP pathogenesis, offering novel mechanistic insight and establishing FABP3 as a promising biomarker and therapeutic target for nephrolithiasis prevention.