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<p>Chronic kidney disease (CKD) is a global health concern characterized by a gradual decline in kidney function. Despite advancements in screening and diagnostic markers for CKD, there remains an urgent need to identify patients in the early stages. In this study, we analyzed human blood and kidney samples and found that selenium-binding protein 1 (SELENBP1) is downregulated in CKD patients, with its levels positively correlating with the estimated glomerular filtration rate (eGFR). To further explore the role of SELENBP1 in renal fibrosis, we performed high-throughput proteomic analysis using mouse plasma from adenine diet-induced mice with kidney failure. The results showed that SELENBP1 was significantly downregulated in both plasma and kidney samples from mice at early and late CKD stages in both adenine diet-induced and unilateral ureter obstruction (UUO) mouse models, aligning with findings from human samples. <i>In vitro</i> experiments utilizing human renal proximal tubular HK-2 cells revealed that <i>SELENBP1</i> knockdown promoted fibrosis, whereas its overexpression inhibited fibrotic processes. Moreover, nuclear magnetic resonance (NMR) spectroscopy indicated that plasma dimethyl sulfone (DMSO<sub>2</sub>) levels increased progressively with CKD advancement. By knocking down <i>SELENBP1</i> in HK-2 cells, we demonstrated that the absence of SELENBP1 inhibits H<sub>2</sub>S production, thereby impairing its protective function in the kidneys. A coupled enzyme assay further confirmed a marked decrease in H<sub>2</sub>S levels in <i>SELENBP1</i> knockdown cells, underscoring the critical role of SELENBP1 in H<sub>2</sub>S generation via MT metabolism. Our findings unveil SELENBP1’s role in mitigating renal fibrosis, opening new avenues for further research into SELENBP1 as a potential therapeutic target in CKD and renal fibrosis.</p>

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SELENBP1 protects against kidney fibrosis in chronic kidney disease as a methanethiol oxidase

  • 期刊论文

  • 发表日期：

    2025年8月22日

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  • Yue Zhang,
  • Dongqing Zha,
  • Caixiang Liu,
  • Wan Yang,
  • Yiyi Zuo,
  • Jie Jiang,
  • Yan Gong,
  • Qing He

摘要

Chronic kidney disease (CKD) is a global health concern characterized by a gradual decline in kidney function. Despite advancements in screening and diagnostic markers for CKD, there remains an urgent need to identify patients in the early stages. In this study, we analyzed human blood and kidney samples and found that selenium-binding protein 1 (SELENBP1) is downregulated in CKD patients, with its levels positively correlating with the estimated glomerular filtration rate (eGFR). To further explore the role of SELENBP1 in renal fibrosis, we performed high-throughput proteomic analysis using mouse plasma from adenine diet-induced mice with kidney failure. The results showed that SELENBP1 was significantly downregulated in both plasma and kidney samples from mice at early and late CKD stages in both adenine diet-induced and unilateral ureter obstruction (UUO) mouse models, aligning with findings from human samples. In vitro experiments utilizing human renal proximal tubular HK-2 cells revealed that SELENBP1 knockdown promoted fibrosis, whereas its overexpression inhibited fibrotic processes. Moreover, nuclear magnetic resonance (NMR) spectroscopy indicated that plasma dimethyl sulfone (DMSO2) levels increased progressively with CKD advancement. By knocking down SELENBP1 in HK-2 cells, we demonstrated that the absence of SELENBP1 inhibits H2S production, thereby impairing its protective function in the kidneys. A coupled enzyme assay further confirmed a marked decrease in H2S levels in SELENBP1 knockdown cells, underscoring the critical role of SELENBP1 in H2S generation via MT metabolism. Our findings unveil SELENBP1’s role in mitigating renal fibrosis, opening new avenues for further research into SELENBP1 as a potential therapeutic target in CKD and renal fibrosis.