2. Academic Validation
  3. rhBNP inhibited ferroptosis in renal ischemia-reperfusion injury through promoting selenium recycling

rhBNP inhibited ferroptosis in renal ischemia-reperfusion injury through promoting selenium recycling

  • Free Radic Biol Med. 2025 Dec 31:245:283-300. doi: 10.1016/j.freeradbiomed.2025.12.055.
Meiying Huang 1,  Luhao Wang 2,  Minghui Wang 3,  Xi Yuan 3,  Meng Li 3,  Luosha Long 3,  Xinyan Wu 4,  Long Xu 3,  Xiaoduo Zhao 4,  Baien Liang 4,  Xiangdong Guan 2,  Weidong Wang 5,  Chunling Li 6,  Jianfeng Wu 7
Affiliations

Affiliations

  • 1 Department of Critical Care Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China; Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
  • 2 Department of Critical Care Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
  • 3 Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China; Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
  • 4 Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China; Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
  • 5 Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China; Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China. Electronic address: [email protected].
  • 6 Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China; Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China. Electronic address: [email protected].
  • 7 Department of Critical Care Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. Electronic address: [email protected].
PMID: 41482081 DOI: 10.1016/j.freeradbiomed.2025.12.055
Abstract

Renal ischemia-reperfusion (IR) injury is a major cause of acute kidney injury (AKI), with limited specific therapies. Recombinant human brain natriuretic peptide (rhBNP) shows potential renal protective effects, but its role and mechanism in IR-induced AKI is unclear. The present study showed rhBNP improved renal function recovery and reduced AKI progression in ICU patients. In rat IR models, rhBNP alleviated tubular injury and enhanced kidney function. Selenocysteine lyase (SCLY), an enzyme critical for selenium recycling and selenoprotein synthesis, was identified as the hub gene associated with rhBNP treatment by transcriptome Sequencing. rhBNP treatment markedly upregulated the expression of SCLY in rat kidneys with elevated selenium levels. rhBNP also inhibited Ferroptosis and Apoptosis in the kidney, which was significantly reversed by the knockdown of SCLY. SCLY silencing blocked the protective effect of rhBNP on human HK2 cells subjected to CCCP-R (carbonyl cyanide 3-chlorophenylhydrazone induced ATP depletion-repletion), while SCLY overexpression enhanced it. rhBNP modulated SCLY expression likely through inhibiting the binding of active GTPase RhoA to SCLY protein. In conclusion, rhBNP prevented IR-induced AKI through inhibiting Ferroptosis by upregulating SCLY level and promoting selenium recycling, presenting a potentially new target for AKI treatment.

Keywords

Ferroptosis; Recombinant human brain natriuretic peptide; Renal ischemia-reperfusion injury; Selenocysteine lyase.

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