ArticleCell death & disease2014
Serpina3n accelerates tissue repair in a diabetic mouse model of delayed wound healing.
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 98 citations in OpenAlex.
- Article
- Circular RNAs in Diabetic Foot Ulcers: A Scoping Review of Clinical, Preclinical, and In Silico Evidence on Diagnostic and Therapeutic Potentials.Endocrinology, diabetes & metabolism · 2026Article
- Limited effect of surfactant protein D ablation on doxorubicin-induced intestinal toxicity in mice.Frontiers in immunology · 2026Article
- Dynamic transcriptomic profiling of dorsal root ganglia reveals stage-specific mechanisms in diabetic neuropathic pain.Frontiers in molecular neuroscience · 2026Article
- Role of SerpinA3 in the Pathogenesis of Graves' Orbitopathy in Orbital Fibroblasts.Investigative ophthalmology & visual science · 2025Article
- Transcriptomic analysis of bone transport reveals different functions between both ends.Frontiers in physiology · 2025Article
- Clearance of p21 highly expressing senescent cells accelerates cutaneous wound healing.Nature aging · 2025Article
- Sensory nerve-secreted factors regulate basal keratinocyte functionIntegrative organismal biology (Oxford, England) · 2025Article
- Granzyme serine proteases in inflammation and rheumatic diseases.Nature reviews. Rheumatology · 2024Review
- Potential implications of granzyme B in keloids and hypertrophic scars through extracellular matrix remodeling and latent TGF-β activation.Frontiers in immunology · 2024Article
- Serpina3n/serpina3 alleviates cyclophosphamide-induced interstitial cystitis by activating the Wnt/β-catenin signal.International urology and nephrology · 2023Article
- The importance of inflammation control for the treatment of chronic diabetic wounds.International wound journal · 2023Review
- Astrocyte-derived SerpinA3N promotes neuroinflammation and epileptic seizures by activating the NF-κB signaling pathway in mice with temporal lobe epilepsy.Journal of neuroinflammation · 2023Article
- Fibronectin in hyperglycaemia and its potential use in the treatment of diabetic foot ulcers: A review.International wound journal · 2023Review
- Multifunctional Microgel-Based Cream Hydrogels for Postoperative Abdominal Adhesion Prevention.ACS nano · 2023Article
- Identification of Hub Genes in the Remodeling of Non-Infarcted Myocardium Following Acute Myocardial Infarction.Journal of cardiovascular development and disease · 2022Article
- Expression of the GZMB Gene Polymorphism, SNP rs8192917, in 990 Han Chinese Patients with Postoperative Keloids.Medical science monitor : international medical journal of experimental and clinical research · 2022Article
- Dissecting the cellular landscape and transcriptome network in viral myocarditis by single-cell RNA sequencing.iScience · 2022Article
- Host tissue proteomics reveal insights into the molecular basis of Schistosoma haematobium-induced bladder pathology.PLoS neglected tropical diseases · 2022Article
- Potential role of extracellular granzyme B in wet age-related macular degeneration and fuchs endothelial corneal dystrophy.Frontiers in pharmacology · 2022Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic, non-healing wounds are a major complication of diabetes and are characterized by chronic inflammation and excessive protease activity. Although once thought to function primarily as a pro-apoptotic serine protease, granzyme B (GzmB) can also accumulate in the extracellular matrix (ECM) during chronic inflammation and cleave ECM proteins that are essential for proper wound healing, including fibronectin. We hypothesized that GzmB contributes to the pathogenesis of impaired diabetic wound healing through excessive ECM degradation. In the present study, the murine serine protease inhibitor, serpina3n (SA3N), was administered to excisional wounds created on the dorsum of genetically induced type-II diabetic mice. Wound closure was monitored and skin wound samples were collected for analyses. Wound closure, including both re-epithelialization and contraction, were significantly increased in SA3N-treated wounds. Histological and immunohistochemical analyses of SA3N-treated wounds revealed a more mature, proliferative granulation tissue phenotype as indicated by increased cell proliferation, vascularization, fibroblast maturation and differentiation, and collagen deposition. Skin homogenates from SA3N-treated wounds also exhibited greater levels of full-length intact fibronectin compared with that of vehicle wounds. In addition, GzmB-induced detachment of mouse embryonic fibroblasts correlated with a rounded and clustered phenotype that was prevented by SA3N. In summary, topical administration of SA3N accelerated wound healing. Our findings suggest that GzmB contributes to the pathogenesis of diabetic wound healing through the proteolytic cleavage of fibronectin that is essential for normal wound closure, and that SA3N promotes granulation tissue maturation and collagen deposition.
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