ArticleGraefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie2018
Combined VEGF/PDGF inhibition using axitinib induces αSMA expression and a pro-fibrotic phenotype in human pericytes.
Article in Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 17 citations in OpenAlex.
- Single-Cell Morphomechanics of Prostate Cancer-Associated Fibroblasts Identifies Distinct Features Associated with Patient Outcome.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Feasibility analysis of Sinomenine alleviating fibrosis of filtering bleb after glaucoma filtering surgery: a mini review.Frontiers in medicine · 2025Review
- Exploring the role of granzyme B in subretinal fibrosis of age-related macular degeneration.Frontiers in immunology · 2024Review
- Diabetes Induces Cardiac Fibroblast Activation, Promoting a Matrix-Preserving Nonmyofibroblast Phenotype, Without Stimulating Pericyte to Fibroblast Conversion.Journal of the American Heart Association · 2023Article
- Pharmacological action ofFrontiers in pharmacology · 2023Review
- Axitinib targets cardiac fibrosis in pressure overload-induced heart failure through VEGFA-KDR pathway.Frontiers in medicine · 2023Article
- Review
- Anti-angiogenic properties of rapamycin on human retinal pericytes in an in vitro model of neovascular AMD via inhibition of the mTOR pathway.BMC ophthalmology · 2022Article
- A systems genetics approach to revealing theMolecular vision · 2020Article
- Shaping Up the Tumor Microenvironment With Cellular Fibronectin.Frontiers in oncology · 2020Review
- Metabolic Coordination of Pericyte Phenotypes: Therapeutic Implications.Frontiers in cell and developmental biology · 2020Review
- Isolation of Myoepithelial Cells from Adult Murine Lacrimal and Submandibular Glands.Journal of visualized experiments : JoVE · 2019Article
- Review
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeLarge trials on anti-VEGF/PDGF (vascular endothelial/platelet-derived growth factor) combination therapy have been established to improve management of neovascular activity in age-related macular degeneration. Targeting pericytes, PDGF is thought to induce vessel regression and reduce fibrovascular scarring. The fate of pericytes exposed to anti-VEGF/PDGF combination therapy is not clear. Therefore, this study was designed to study the influence of anti-VEGF/PDGF on pericyte phenotype and cellular behavior.
methodsHuman pericytes from placenta (hPC-PL) were treated with axitinib, a tyrosine kinase inhibitor targeting VEGFR1-3 and PDGFR. Toxic effects were excluded using live/dead staining. Phenotypic changes were evaluated using phalloidin staining for actin cytoskeleton and the expression of stress fibers. MRNA and protein expression levels of α-smooth muscle actin (αSMA) as a marker of proto-myofibroblastic transition were evaluated with real-time PCR and Western blotting. Influences of fibrotic cellular mechanisms were evaluated with a scratch wound migration and a collagen gel contraction assay.
resultsTreatment with 0.5, 1, and 2.5 μg/ml axitinib strongly induced a proto-myofibroblast-like actin cytoskeleton with a marked increase in stress fibers. Quantitative real-time PCR and Western blotting revealed these changes to be linked to dose-dependent increases in αSMA mRNA and protein expression. However, fibrotic cellular mechanisms were significantly reduced in the presence of axitinib (scratch wound closure: up to - 78.4%, collagen gel contraction: up to - 37.4%).
conclusionsCombined anti-VEGF/PDGF inhibition seems to induce a proto-myofibroblast-like phenotype in human pericytes in vitro, but reduce profibrotic cellular mechanisms due to prolonged anti-PDGF inhibition.
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