ArticleEMBO molecular medicine2020
Inhibition of Sema4D/PlexinB1 signaling alleviates vascular dysfunction in diabetic retinopathy.
Article in EMBO molecular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 73 citations in OpenAlex.
- Stage-dependent signaling networks and therapeutic strategies in diabetic retinopathy: from neurovascular dysfunction to angiogenesis and fibrosis.Molecular biology reports · 2026Review
- Pharmacological manipulation of Sema4D by salvianolic acid A mitigates diabetic retinopathy via inhibiting PlexinB1/RhoA/ROCK/pMLC2 signaling cascade involved in endothelial dysfunction.Chinese medicine · 2026Article
- Investigation of the causal effect and molecular signatures of serum hydroxyvitamin D on atherosclerosis: a Mendelian randomization and transcriptomic approach.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2026Article
- Proteolytic remodelling of the extracellular matrix by pericytes.The FEBS journal · 2026Review
- Tumor-Derived Exosomal TAGLN2 Promotes Metastasis by Inducing Vascular Permeability and Angiogenesis via the NRP1/SEMA4D/YAP Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Soluble Sema4D From γδ T Cells Exerts Osteoblast Inhibition via Plexin-B/mTOR Signalling Contributing to Pathogenesis of Bisphosphonate-Related Osteonecrosis of the Jaws.Cell proliferation · 2026Article
- Serum Semaphorin Alterations in Psoriasis: Links to Metabolic Status Rather than Disease Severity.Metabolites · 2026Article
- CD36 Regulates PANoptosis in Diabetic Retinopathy via the NOTCH/MAML Pathway.Journal of diabetes research · 2026Article
- Nanomaterial-enabled delivery of plant-derived bioactive metabolites for diabetic retinopathy: from evidence appraisal to preclinical translation.Frontiers in pharmacology · 2026Review
- Research article proteomics-based plasma biomarkers for predicting CRKP infection in ICU sepsis patients.Frontiers in pharmacology · 2026Article
- Association of inflammatory scoring tools with spirometry indices in COVID-19 patients: a single center cohort study.Iranian journal of microbiology · 2025Article
- Ginkgo Biloba extract attenuates diabetic retinopathy progression by modulating TP53 ubiquitination in a rat model.Molecular biology reports · 2025Article
- Article
- Obesity drives depot-specific vascular remodeling in male white adipose tissue.Nature communications · 2025Article
- Smoking aggravates neovascular age-related macular degeneration via Sema4D-PlexinB1 axis-mediated activation of pericytes.Nature communications · 2025Article
- TTK Inhibition Alleviates Postinjury Neointimal Formation and Atherosclerosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The role of transcytosis in the blood-retina barrier: from pathophysiological functions to drug delivery.Frontiers in pharmacology · 2025Review
- ELAVL1 Stabilizes HMOX1 mRNA to Drive Ferroptosis in Diabetic Retinopathy.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Article
- Autophagy-dependent ferroptosis may play a critical role in early stages of diabetic retinopathy.World journal of diabetes · 2024Review
- Protein O-GlcNAcylation coupled to Hippo signaling drives vascular dysfunction in diabetic retinopathy.Nature communications · 2024Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
Diabetic retinopathy (DR) is a common complication of diabetes and leads to blindness. Anti-VEGF is a primary treatment for DR. Its therapeutic effect is limited in non- or poor responders despite frequent injections. By performing a comprehensive analysis of the semaphorins family, we identified the increased expression of Sema4D during oxygen-induced retinopathy (OIR) and streptozotocin (STZ)-induced retinopathy. The levels of soluble Sema4D (sSema4D) were significantly increased in the aqueous fluid of DR patients and correlated negatively with the success of anti-VEGF therapy during clinical follow-up. We found that Sema4D/PlexinB1 induced endothelial cell dysfunction via mDIA1, which was mediated through Src-dependent VE-cadherin dysfunction. Furthermore, genetic disruption of Sema4D/PlexinB1 or intravitreal injection of anti-Sema4D antibody reduced pericyte loss and vascular leakage in STZ model as well as alleviated neovascularization in OIR model. Moreover, anti-Sema4D had a therapeutic advantage over anti-VEGF on pericyte dysfunction. Anti-Sema4D and anti-VEGF also conferred a synergistic therapeutic effect in two DR models. Thus, this study indicates an alternative therapeutic strategy with anti-Sema4D to complement or improve the current treatment of DR.
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