Dear Editor,
This study 1 offers valuable insights into cordycepin's role in diabetic nephropathy (DN), particularly its modulation of ferroptosis via SLC7A11/GPX4. However, three critical concerns warrant attention to strengthen clinical applicability and mechanistic depth. First, the exclusive use of high‐glucose (HG)‐treated MPC5 cells and streptozotocin (STZ)‐induced diabetic mice limits translational relevance. STZ models mimic type 1 diabetes, while DN predominantly complicates type 2 diabetes (T2D), which involves insulin resistance and heterogeneous renal pathology not captured here 2 . Human podocytes or patient‐derived cells would better reflect DN pathophysiology. Second, the SLC7A11/GPX4 axis is presented in isolation, neglecting crosstalk with established DN pathways like nuclear factor erythroid 2‐related factor 2 (Nrf2). Nrf2 regulates GPX4 and ferroptosis in DN but was unexplored 3 . Validating interactions using Nrf2 inhibitors (e.g., ML385) could clarify the mechanistic hierarchy. Third, the cordycepin dose (400 mg/kg in mice) raises safety concerns. This far exceeds typical human‐equivalent doses (~3–6 mg/kg) and lacks supporting toxicity data 4 . Dose–response studies in T2D models (e.g., db/db mice) and renal/hepatic safety assays are essential.
To address these gaps, future work should prioritize human cell lines, incorporate T2D models, and probe Nrf2‐SLC7A11/GPX4 crosstalk. Additionally, lower cordycepin doses with toxicity profiling would enhance therapeutic feasibility. These steps may bridge mechanistic findings to clinical practice, aligning with precision medicine approaches for DN 5 .
DISCLOSURE
The author declares no conflict of interest.
Approval of the research protocol: N/A.
Informed consent: N/A.
Approval date of registry and the registration no. of the study/trial: N/A.
Animal studies: N/A.
Linked Articles
This article is linked to https://doi.org/10.1111/jdi.14407.
DATA AVAILABILITY STATEMENT
There is no original data for this letter to the editor.
References
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
There is no original data for this letter to the editor.