ArticleInvestigative ophthalmology & visual science2012
uPA binding to PAI-1 induces corneal myofibroblast differentiation on vitronectin.
Article in Investigative ophthalmology & visual science, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 16 citations in OpenAlex.
- Plasminogen Activation System and Fibroblasts: Impact on Tissue Remodeling, Disease, and Organ Homeostasis.Inflammation · 2026Review
- Review
- Review
- The uPA/uPAR System Orchestrates the Inflammatory Response, Vascular Homeostasis, and Immune System in Fibrosis Progression.International journal of molecular sciences · 2023Review
- Urokinase plasminogen activator predicts poor prognosis in hepatocellular carcinoma.Journal of gastrointestinal oncology · 2021Article
- Adipose-PAS interactions in the context of its localised bio-engineering potential (Review).Biomedical reports · 2021Review
- Wnt/β-catenin pathway and cell adhesion deregulation in CSDE1-related intellectual disability and autism spectrum disorders.Molecular psychiatry · 2021Article
- Vitronectin deficiency attenuates hepatic fibrosis in a non-alcoholic steatohepatitis-induced mouse model.International journal of experimental pathology · 2019Article
- SLURP-1 modulates corneal homeostasis by serving as a soluble scavenger of urokinase-type plasminogen activator.Investigative ophthalmology & visual science · 2014Article
- Vitronectin-binding PAI-1 protects against the development of cardiac fibrosis through interaction with fibroblasts.Laboratory investigation; a journal of technical methods and pathology · 2014Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
purposeVitronectin (VN) in provisional extracellular matrix (ECM) promotes cell migration. Fibrotic ECM also includes VN and, paradoxically, strongly adherent myofibroblasts (Mfs). Because fibrotic Mfs secrete elevated amounts of urokinase plasminogen activator (uPA), we tested whether increased extracellular uPA promotes the persistence of Mfs on VN.
methodsPrimary human corneal fibroblasts (HCFs) were cultured in supplemented serum-free medium on VN or collagen (CL) with 1 ng/mL transforming growth factor β1 (TGFβ1). Adherent cells were quantified using crystal violet. Protein expression was measured by Western blotting and flow cytometry. Transfection of short interfering RNAs was performed by nucleofection. Mfs were identified by α-smooth muscle actin (α-SMA) stress fibers. Plasminogen activator inhibitor (PAI-1) levels were quantified by ELISA.
resultsTGFβ1-treated HCFs secreted PAI-1 (0.5 uM) that bound to VN, competing with αvβ3/αvβ5 integrin/VN binding, thus promoting cell detachment from VN. However, addition of uPA to cells on VN increased Mf differentiation (9.7-fold), cell-adhesion (2.2-fold), and binding by the VN integrins αvβ3 and -β5 (2.2-fold). Plasmin activity was not involved in promoting these changes, as treatment with the plasmin inhibitor aprotinin had no effect. A dominant negative PAI-1 mutant (PAI-1R) that binds to VN but does not inhibit uPA prevented the increase in uPA-stimulated cell adhesion and reduced uPA-stimulated integrin αvβ3/αvβ5 binding to VN by 73%.
conclusionsuPA induction of TGFβ1-dependent Mf differentiation on VN supports the hypothesis that elevated secretion of uPA in fibrotic tissue may promote cell adhesion and the persistence of Mfs. By blocking uPA-stimulated cell adhesion, PAI-1R may be a useful agent in combating corneal scarring.
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