Hirudin ameliorates diabetic nephropathy by inhibiting Gsdmd-mediated pyroptosis

Our group previously reported that hirudin ameliorated diabetic nephropathy (DN) in streptozotocin (STZ)-injected rats, but the mechanism remained largely unknown. Therefore, we further explored its possible mechanism. We subcutaneously injected 5 U hirudin into STZ-induced WT mice or Gasdermin D (Gsdmd)-/- (KO) mice daily for 12 weeks, respectively, and evaluated their kidney injury. Next, glomerular endothelial cells (GECs), renal tubular epithelial cells (RTECs), and bone-marrow-derived macrophages (BMDMs) were isolated from WT mice and treated with hirudin in the presence of high glucose/lipopolysaccharides and ATP to measure the release of interleukin-18 and interleukin-1β. Kidney injury induced by STZ injection was significantly ameliorated by hirudin through inhibiting Gsdmd-mediated pyroptosis in the mice, not Caspase 1-mediated apoptosis. Meanwhile, hirudin also suppressed pyroptosis in primary GECs, RTECs, and BMDMs in vitro. Moreover, the deletion of Gsdmd reduced pyroptosis and kidney injury both in vivo and in vitro. We also found that hirudin regulated the expression of Gsdmd by inhibiting interferon regulatory factor 2 (Irf2). Hirudin ameliorated Gsdmd-mediated pyroptosis by inhibiting irf2, leading to the improvement of kidney injury. Therefore, hirudin might serve as a potential therapeutic strategy to treat DN.

Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.

Our group previously reported that hirudin ameliorated diabetic nephropathy (DN) in streptozotocin (STZ)-injected rats, but the mechanism remained largely unknown.

Explore how this research connects to clinical practice

More peer-reviewed studies in Drug Development.

• Novel Leech Antimicrobial Peptides — Hirunipins — Kumar et al. (2025)
• Medicinal Leech Genome Assembly — Anticoagulant Gene Catalog — Kvist et al. (2020)
• BRIGHT-4 Trial — Bivalirudin vs Heparin by BMI — BRIGHT-4 Investigators (2025)
• RE-LY Trial — Dabigatran vs Warfarin in Atrial Fibrillation — Connolly SJ et al. (2009)
• Hirudin Disrupts Breast Cancer CTC Clusters — Anti-Metastatic Potential — Research team (2025) (2025)
• Novel CRA Protein from Hirudo medicinalis — Complement Regulation — Research team (2025) (2025)
• Hirunipin-2 — Second-Generation Leech Antimicrobial Peptide — Kumar et al. (2025)
• Effects of hirudotherapy on liver functions, lipid profile, and insulin sensitivity in rats with metabolic syndrome — Bilden A et al. (2026)
• Hirudotherapy in Medicine and Dentistry — Jha K et al. (2015)
• Medicinal leech therapy (hirudotherapy): a brief overview — Singh A (2010)