Hirudin ameliorates diabetic nephropathy by inhibiting Gsdmd-mediated pyroptosis
Basic science / preclinical published in Cell biology and toxicology (2023)
Abstract
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.
Resumen
Our group previously reported that hirudin ameliorated diabetic nephropathy (DN) in streptozotocin (STZ)-injected rats, but the mechanism remained largely unknown.
Por qué esto importa para la hirudoterapia
Este estudio investigó el mecanismo por el cual hirudin mejora la nefropatía diabética, administrando hirudin subcutáneo diario a ratones de tipo silvestre y knockout para Gasdermin D (Gsdmd) con diabetes inducida por estreptozotocina durante 12 semanas, y realizando experimentos in vitro paralelos en células endoteliales glomerulares primarias, células epiteliales tubulares renales y macrófagos derivados de médula ósea. Los autores informan que hirudin redujo la lesión renal al suprimir la piroptosis mediada por Gsdmd mediante la inhibición del factor regulador de interferón 2 (Irf2), y no a través de la apoptosis mediada por caspasa 1. Hirudin es un agente clave en la hirudoterapia, y este trabajo describe una vía mecanística por la cual podría proteger el tejido renal. Sin embargo, la relevancia para la terapia clínica con sanguijuelas es limitada e indirecta: el estudio utilizó hirudin inyectado en modelos de roedores y de cultivo celular —no se utilizaron sanguijuelas, saliva de sanguijuela ni sujetos humanos— y los hallazgos siguen siendo preclínicos.
Citación
Hirudin ameliorates diabetic nephropathy by inhibiting Gsdmd-mediated pyroptosis.
Han J et al. · Cell biology and toxicology, 2023
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Añadido a la biblioteca ASH: March 18, 2026 · Última actualización del sitio: June 18, 2026