ArticleDisease models & mechanisms2018
CD40-mediated HIF-1α expression underlying microangiopathy in diabetic nerve pathology.
Article in Disease models & mechanisms, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- Review
- A machine learning-based predictive model for postoperative pulmonary complications in lung cancer and its SHAP interpretation.Frontiers in oncology · 2026Article
- The pivotal role of immunometabolism in diabetic neuropathy and its potential therapeutic strategies.Frontiers in endocrinology · 2026Review
- Macrophage polarization in diabetic vascular complications: mechanistic insights and therapeutic targets.Journal of translational medicine · 2025Review
- Hypertension is associated with the reduction in epidermal small fibres independently of sural nerve inflammation in type 2 diabetic subjects.Journal of neurochemistry · 2025Article
- The role of novel inflammation-associated biomarkers in diabetic peripheral neuropathy.Metabolism open · 2024Review
- Association of white blood cell count to mean platelet volume ratio with type 2 diabetic peripheral neuropathy in a Chinese population: a cross-sectional study.BMC endocrine disorders · 2024Article
- How inflammation dictates diabetic peripheral neuropathy: An enlightening review.CNS neuroscience & therapeutics · 2024Review
- Article
- Nerve pathology of microangiopathy and thromboinflammation in hereditary transthyretin amyloidosis.Annals of clinical and translational neurology · 2024Article
- Article
- CD40-CD40L in Neurological Disease.International journal of molecular sciences · 2022Review
- HIF-1BioMed research international · 2022Article
- Diabetes mellitus exacerbates experimental autoimmune myasthenia gravis via modulating both adaptive and innate immunity.Journal of neuroinflammation · 2021Article
- Neurobiological Opportunities in Diabetic Polyneuropathy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Review
- Blood-Nerve Barrier (BNB) Pathology in Diabetic Peripheral Neuropathy and In Vitro Human BNB Model.International journal of molecular sciences · 2020Review
- SP6616 as a Kv2.1 inhibitor efficiently ameliorates peripheral neuropathy in diabetic mice.EBioMedicine · 2020Article
- Sural Nerve Perfusion in Mice.Frontiers in neuroscience · 2020Article
- PPARγ: the dominant regulator among PPARs in dry eye lacrimal gland and diabetic lacrimal gland.International journal of ophthalmology · 2020Article
- Functional and Structural Changes of the Blood-Nerve-Barrier in Diabetic Neuropathy.Frontiers in neuroscience · 2018Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To understand the pathology and molecular signatures of microangiopathy in diabetic neuropathy, we systemically and quantitatively examined the morphometry of microvascular and nerve pathologies of sural nerves. In the endoneurium of diabetic nerves, prominent microangiopathy was observed, as evidenced by reduced capillary luminal area, increased capillary basement membrane thickness and increased proportion of fibrin(+) blood vessels. Furthermore, capillary basement membrane thickness and the proportion of fibrin(+) blood vessels were correlated with small myelinated fiber density in diabetic nerves. In diabetic nerves, there was also significant macrophage and T cell infiltration, and cluster of differentiation 40 (CD40) expression was increased. The molecular alterations observed were upregulation of hypoxia-inducible factor-1α (HIF-1α), mitogen-activated protein kinase-activated protein kinase 2 (MK2; MAPKAPK2) and phosphatase and tensin homolog (PTEN). In addition, HIF-1α was correlated with small myelinated fiber density and capillary luminal area, while both MK2 and PTEN were correlated with capillary basement membrane thickness. The molecular cascades were further demonstrated and replicated in a cell model of microangiopathy on human umbilical vein endothelial cells (HUVECs) exposed to high-glucose medium by silencing of CD40, PTEN and HIF-1α in HUVECs using shRNA. These data clarified the hierarchy of the molecular cascades, i.e. upregulation of CD40 leading to HIF-1α expression in endothelium and nerve fibers. In conclusion, this study revealed the association of microangiopathy, thrombosis and inflammatory infiltrates with nerve degeneration in diabetic nerves, demonstrating that CD40 is a key molecule for the upregulation of HIF-1α and PTEN underlying the severity of microangiopathy.
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