Scholarlink

<p>Nephrolithiasis is a highly prevalent urological condition with a marked recurrence tendency. However, the molecular mechanisms within the local renal tissue microenvironment remain unclear—largely due to the limited availability of relevant clinical specimens, which has hindered in-depth research efforts. In this study, we conducted label-free quantitative proteomics on paired stone-containing (S) and non-stone (NS) renal papillary tissues. All these samples were obtained from 6 patients with calcium oxalate stones. To reliably identify differentially expressed proteins (DEPs), we employed two statistical models simultaneously: unpaired analysis (fold change |FC| ≥ 1.2, <i>p</i> &lt; 0.05) and patient-specific paired analysis (|FC| ≥ 1.5, <i>p</i> &lt; 0.05). Group-wise comparison identified a total of 41 DEPs. Subsequent pathway analysis showed that these DEPs were associated with several key biological processes, including extracellular matrix interaction, oxidative phosphorylation, and glycosaminoglycan metabolism. Notably, paired analysis across individuals revealed a shared core of dysregulated proteins. Interestingly, LPCAT3 exhibited altered expression in all 6 patients; in contrast, RPUSD2, SLC34A3, UCK1, ERVK-19, and ACSL5 were dysregulated in 5 patients. This recurrent signature suggests the existence of convergent pathological mechanisms, roughly involving dysregulated lipid metabolism (LPCAT3, ACSL5), disrupted phosphate homeostasis (SLC34A3), abnormal nucleotide metabolism (UCK1), mitochondrial dysfunction (RPUSD2), and inflammatory responses (ERVK-19). Our study delineates the proteomic landscape of the stone-containing renal microenvironment in humans and uncovers a robust, patient-shared molecular signature. These recurrent core proteins—particularly LPCAT3—hold promise as novel therapeutic targets for preventing stone recurrence by targeting underlying local pathological processes, which offers new insights and directions for clinical intervention.</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

Proteomic analysis of stone-containing and non-stone human renal papillae reveals novel insights and therapeutic targets

  • 期刊论文

  • 发表日期：

    2026年2月12日

查看全文
  • Yiying Jia,
  • Meng Shu,
  • Shuwei Zhang,
  • Minjie Chen,
  • Ziyu Fang,
  • Xiaofeng Gao

摘要

Nephrolithiasis is a highly prevalent urological condition with a marked recurrence tendency. However, the molecular mechanisms within the local renal tissue microenvironment remain unclear—largely due to the limited availability of relevant clinical specimens, which has hindered in-depth research efforts. In this study, we conducted label-free quantitative proteomics on paired stone-containing (S) and non-stone (NS) renal papillary tissues. All these samples were obtained from 6 patients with calcium oxalate stones. To reliably identify differentially expressed proteins (DEPs), we employed two statistical models simultaneously: unpaired analysis (fold change |FC| ≥ 1.2, p < 0.05) and patient-specific paired analysis (|FC| ≥ 1.5, p < 0.05). Group-wise comparison identified a total of 41 DEPs. Subsequent pathway analysis showed that these DEPs were associated with several key biological processes, including extracellular matrix interaction, oxidative phosphorylation, and glycosaminoglycan metabolism. Notably, paired analysis across individuals revealed a shared core of dysregulated proteins. Interestingly, LPCAT3 exhibited altered expression in all 6 patients; in contrast, RPUSD2, SLC34A3, UCK1, ERVK-19, and ACSL5 were dysregulated in 5 patients. This recurrent signature suggests the existence of convergent pathological mechanisms, roughly involving dysregulated lipid metabolism (LPCAT3, ACSL5), disrupted phosphate homeostasis (SLC34A3), abnormal nucleotide metabolism (UCK1), mitochondrial dysfunction (RPUSD2), and inflammatory responses (ERVK-19). Our study delineates the proteomic landscape of the stone-containing renal microenvironment in humans and uncovers a robust, patient-shared molecular signature. These recurrent core proteins—particularly LPCAT3—hold promise as novel therapeutic targets for preventing stone recurrence by targeting underlying local pathological processes, which offers new insights and directions for clinical intervention.