What this means
Researchers found a treated protein reduced kidney damage and cell death in diabetic mice. This work was in mice and cells, so it does not show the same effect in people.
Plain-English summary written by an AI model from the abstract. The original is below.
- Who it was tested in
- Diabetic mice, two other mouse models, human kidney cells in a lab, and kidney tissue from DN patients
- Kind of research
- A study
The science
- Original title
- S14G-humanin (HNG) ameliorates diabetic nephropathy tubular injury by inhibiting Z-DNA/ZBP1-mediated necroptosis.
- Authors
- Liu Y, Hu C, Luo S et al.
- Journal
- European journal of pharmacology
- Published
- Jul 23, 2026
- Study type
- Study · in humans
- PMID
- 42492881 ↗
Abstract
Background
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease, with limited therapeutic options. S14G-humanin (HNG), a potent analog of humanin, exerts protective effects in various diseases, but its role in DN remains unexplored.
What they did
DN was induced in C57BL/6 mice via high-fat diet and streptozotocin (STZ), with or without HNG treatment. Renal injury, necroptosis, and Z-DNA/ZBP1 pathways were evaluated by histology, western blotting, and transcriptomics, and key findings were validated in db/db mice and high glucose/palmitate (HG + PA)-treated HK-2 cells.
What they found
HNG treatment dose-dependently alleviated renal injury in DN mice. Specifically, high-dose-HNG significantly reduced the urinary albumin-to-creatinine ratio (UACR) by 49.5% (from 103.91 ± 7.68 to 52.50 ± 4.02 μg/mg, P < 0.001) and alleviated renal pathological injury compared to untreated DN mice. Mechanistically, transcriptomics and immunoblotting revealed that HNG markedly inhibited tubular necroptosis, as evidenced by a 52.2% reduction in p-MLKL expression (P < 0.001). HNG also suppressed mitochondrial BAX translocation, reduced mitochondrial ROS production, and blocked mitochondrial Z-DNA leakage, which consequently abrogated ZBP-1 upregulation and ZBP1-mediated necroptosis. These protective effects were corroborated in db/db diabetic mice and HG + PA-challenged HK-2 tubular cells. Moreover, ZBP1 was markedly upregulated, with increased p-MLKL expression in renal tubules of DN patients compared to controls (P < 0.05). HNG ameliorates DN tubular injury by inhibiting BAX-driven mitochondrial oxidative stress and subsequent Z-DNA/ZBP1-mediated necroptosis, highlighting HNG as a promising therapeutic candidate for DN.
The authors' abstract, grouped under plain headings from its own section labels.
Liu Y, Hu C, Luo S et al. S14G-humanin (HNG) ameliorates diabetic nephropathy tubular injury by inhibiting Z-DNA/ZBP1-mediated necroptosis. European journal of pharmacology. 2026. doi:10.1016/j.ejphar.2026.179175. PMID: 42492881. https://pubmed.ncbi.nlm.nih.gov/42492881/
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