June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Extracellular vimentin secreted in response to injury induces emergence of fibrosis-causing myofibroblasts
Author Affiliations & Notes
  • Janice L Walker
    Pathology/Anatomy&Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, United States
    Ophthalmology, Thomas Jefferson University , Philadelphia, Pennsylvania, United States
  • Alhanoof A Alnwibit
    Pathology/Anatomy&Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, United States
  • Alison R Romisher
    Pathology/Anatomy&Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, United States
  • Brigid Bleaken
    Pathology/Anatomy&Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, United States
  • A Sue Menko
    Pathology/Anatomy&Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, United States
    Ophthalmology, Thomas Jefferson University , Philadelphia, Pennsylvania, United States
  • Footnotes
    Commercial Relationships   Janice Walker, None; Alhanoof Alnwibit, None; Alison Romisher, None; Brigid Bleaken, None; A Sue Menko, None
  • Footnotes
    Support  NIH Grant EY021784
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 3791. doi:
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    • Get Citation

      Janice L Walker, Alhanoof A Alnwibit, Alison R Romisher, Brigid Bleaken, A Sue Menko; Extracellular vimentin secreted in response to injury induces emergence of fibrosis-causing myofibroblasts
      . Invest. Ophthalmol. Vis. Sci. 2017;58(8):3791.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The vimentin intermediate filament protein can exist as a cytoskeletal filament, as soluble forms that are involved in regulating dynamic cellular processes, and as an extracellular signal. Using an ex vivo mock cataract surgery model for fibrosis we studied whether vimentin regulates the process by which mesenchymal leader cells that respond to injury acquire a myofibroblast phenotype associated with fibrotic disease.

Methods : An ex vivo mock cataract surgery model for tissue injury was used that recapitulates the major features of the lens fibrotic disease Posterior Capsule Opacification (PCO). For these studies we focused on the mesenchymal leader cells that move off the edge of the explant onto the rigid tissue culture substrate and differentiate to myofibroblasts. Vimentin was localized by confocal microscopy following immunofluorescence staining. Extracellular vimentin in the media in response to injury was assessed by Western blot analysis. Presence of vimentin on the cell surface was determined by live immunolabeling and immunolabeling of fixed non-permeabilized cultures, and with biotinylation studies. Vimentin signaling of myofibroblast differentiation was examined with both the vimentin inhibitor Withaferin A (WFA) and monoclonal antibodies to vimentin. Myofibroblast emergence was determined by expression of αSMA.

Results : In studies with our ex vivo lens injury model we discovered that extracellular vimentin was secreted by the cells in response to wounding. This soluble form of vimentin associates with the cell surface of mesenchymal leader cells that become myofibroblasts. WFA, a vimentin inhibitor that targets soluble vimentin prevents myofibroblast emergence. Importantly, exposure of the cultures to two distinct monoclonal antibodies to vimentin also blocked leader cell differentiation to myofibroblasts.

Conclusions : These studies reveal for the first time a role for extracellular vimentin in inducing myofibroblast differentiation associated with fibrotic disease. Moreover, targeting extracellular vimentin with monoclonal antibodies may provide a valuable therapeutic tool for the prevention and treatment of fibrotic disease.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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