ArticleMolecular vision2014
S100A4 is upregulated in proliferative diabetic retinopathy and correlates with markers of angiogenesis and fibrogenesis.
Article in Molecular vision, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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Who cites it
27 citing papers in PubMed, 47 citations in OpenAlex.
- Cherry plum powder alleviates excessive proliferation and inflammation of keratinocytes in psoriasis by reducing N6 methyladenosine-modified S100A4.Journal of molecular histology · 2026Article
- Aqueous humor levels of syndecan-1 and syndecan-4 associated with OCTA metrics in diabetic retinopathy.Frontiers in medicine · 2025Article
- Leveraging the integration of bioinformatics and machine learning to uncover common biomarkers and molecular pathways underlying diabetes and nephrolithiasis.Frontiers in immunology · 2025Article
- Proteomic Analysis of Aqueous Humor in Central Retinal Artery Occlusion: Unveiling Novel Insights Into Disease Pathophysiology.Translational vision science & technology · 2024Article
- Inhibition of TLR4/NF-κB pathway and endoplasmic reticulum stress by overexpressed S100A4 ameliorates retinal ischemia-reperfusion injury of mice.Molecular neurobiology · 2024Article
- Macrophage-Myofibroblast Transition Contributes to Myofibroblast Formation in Proliferative Vitreoretinal Disorders.International journal of molecular sciences · 2023Article
- Changes in aqueous and vitreous inflammatory cytokine levels in proliferative diabetic retinopathy: a systematic review and meta-analysis.Eye (London, England) · 2022Review
- Galectin 1-A Key Player between Tissue Repair and Fibrosis.International journal of molecular sciences · 2022Review
- Protein Profiling of WERI-RB1 and Etoposide-Resistant WERI-ETOR Reveals New Insights into Topoisomerase Inhibitor Resistance in Retinoblastoma.International journal of molecular sciences · 2022Article
- Integrative biology of extracellular vesicles in diabetes mellitus and diabetic complications.Theranostics · 2022Review
- Correlations Between Different Angiogenic and Inflammatory Factors in Vitreous Fluid of Eyes With Proliferative Diabetic Retinopathy.Frontiers in medicine · 2021Article
- Single-cell transcriptome analysis of the Akimba mouse retina reveals cell-type-specific insights into the pathobiology of diabetic retinopathy.Diabetologia · 2020Article
- Inflammatory mediators in the vitreal reflux of patients with diabetic macular edema.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2019Article
- The Proinflammatory and Proangiogenic Macrophage Migration Inhibitory Factor Is a Potential Regulator in Proliferative Diabetic Retinopathy.Frontiers in immunology · 2019Article
- Elevated serum fetuin-A levels are associated with grades of retinopathy in type 2 diabetic patients.International ophthalmology · 2018Article
- Article
- Matrix metalloproteinase-14 is a biomarker of angiogenic activity in proliferative diabetic retinopathy.Molecular vision · 2018Article
- Association of plasma osteopontin with diabetic retinopathy in Asians with type 2 diabetes.Molecular vision · 2018Article
- Role of metastasis-induced protein S100A4 in human non-tumor pathophysiologies.Cell & bioscience · 2017Review
- Association of HMGB1 with oxidative stress markers and regulators in PDR.Molecular vision · 2017Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe calcium-binding protein S100A4 is implicated in cancer cell invasion and metastasis, the stimulation of angiogenesis, the progression of fibrosis, and inflammatory disorders. We investigated the expression of S100A4 and correlated it with clinical disease activity as well as with the levels of osteopontin (OPN), soluble syndecan-1, and vascular endothelial growth factor (VEGF) in proliferative diabetic retinopathy (PDR). To reinforce the findings at the functional level, we examined the expressions of S100A4 and OPN in the retinas of diabetic rats and in human retinal microvascular endothelial cells (HRMECs) following exposure to VEGF and the proinflammatory cytokine tumor necrosis factor-α (TNF-α).
methodsVitreous samples from 30 PDR and 30 nondiabetic patients, epiretinal membranes from 14 patients with PDR, the retinas of rats, and HRMECs were studied by enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, western blot analysis, and co-immunoprecipitation.
resultsELISA revealed a significant increase in the expressions of S100A4, OPN, soluble syndecan-1, and VEGF in vitreous samples from PDR patients compared to nondiabetic controls (p = 0.001; <0.001; <0.001; <0.001, respectively). Significant positive correlations were found between the levels of S100A4, OPN (r = 0.52, p = <0.001), soluble syndecan-1 (r = 0.37, p = 0.012), and VEGF (r = 0.29, p = 0.044). In epiretinal membranes, S100A4 was expressed in the vascular endothelial cells and stromal CD45-expressing leukocytes. A significant positive correlation was detected between the number of blood vessels expressing CD31 and the number of stromal cells expressing S100A4 (r = 0.77, p = 0.001). Western blot analysis revealed a significant increase in the expressions of S100A4 and both intact and cleaved OPN in vitreous samples from PDR patients compared to nondiabetic controls, as well as in the retinas of diabetic rats. Co-immunoprecipitation studies revealed a positive interaction between S100A4 and the receptor for advanced glycation end products (RAGE) in the retinas of diabetic rats. TNF-α-but not VEGF-induced the upregulations of S100A4 and both intact and cleaved OPN in HRMECs.
conclusionsS100A4 represents a valuable vitreous marker molecule in the pathogenesis of PDR and might become a new target for the treatment of PDR.
Indexed as
Identifiers
25253987PMC4160443W47656108What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.