Hirudin delays the progression of diabetic kidney disease by inhibiting glomerular endothelial cell migration and abnormal angiogenesis
Mechanism study published in Biomedicine & Pharmacotherapy (2024)
Abstract
BACKGROUND: In the early stages of diabetic kidney disease (DKD), the pathogenesis involves abnormal angiogenesis in the glomerulus. Hirudin, as a natural specific inhibitor of thrombin, has been shown in previous studies to inhibit the migration of various tumor endothelial cells and abnormal angiogenesis. However, its role in DKD remains unclear. METHODS: The effects of hirudin in DKD were studied using spontaneous type 2 diabetic db/db mice (which develop kidney damage at 8 weeks). Network pharmacology was utilized to identify relevant targets. An in vitro high glucose model was established using mouse glomerular endothelial cells (MGECs) to investigate the effects of hirudin on the migration and angiogenic capacity of MGECs. RESULTS: Hirudin can ameliorate kidney damage in db/db mice. Network pharmacology suggests its potential association with the VEGFA/VEGFR2 pathway. Western blot and immunohistochemistry demonstrated elevated protein expression levels of VEGFA, VEGFR2, AQP1, and CD31 in db/db mice, while hirudin treatment reduced their expression. In the MGECs high glucose model, hirudin may reverse the enhanced migration and angiogenic capacity of MGECs in a high glucose environment by altering the expression of VEGFA, VEGFR2, AQP1, and CD31. Moreover, the drug effect gradually increases with higher concentrations of hirudin. CONCLUSIONS: This study suggests that hirudin can improve early-stage diabetic kidney disease kidney damage by inhibiting the migration and angiogenesis of glomerular endothelial cells, thereby further expanding the application scope of hirudin. Additionally, the study found increased expression of AQP1 in DKD, providing a new perspective for further research on the potential pathogenesis of DKD.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Summary
Hirudin delays diabetic kidney disease in mice by inhibiting glomerular endothelial cell migration and abnormal angiogenesis — additional renoprotective mechanism for leech-hirudin.
Why This Matters for Hirudotherapy
This study explored how hirudin affects early-stage diabetic kidney disease (DKD) by utilizing spontaneous type 2 diabetic db/db mice and in vitro high glucose models of mouse glomerular endothelial cells. It found that hirudin ameliorates kidney damage by downregulating the VEGFA/VEGFR2 pathway, thereby inhibiting abnormal glomerular angiogenesis and endothelial cell migration. For ASH, this highlights a novel anti-angiogenic mechanism of a well-known leech secretome component, suggesting broader therapeutic potentials. The primary limitation is that these are preclinical, mechanistic findings from animal and cell models, which do not establish clinical efficacy or safety for hirudotherapy in human diabetic patients.
Citation
Hirudin delays the progression of diabetic kidney disease by inhibiting glomerular endothelial cell migration and abnormal angiogenesis.
Zhang J et al. · Biomedicine & pharmacotherapy, 2024
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