Damage-induced reactive oxygen species regulate vimentin and dynamic collagen-based projections to mediate wound repair

Abstract

Tissue injury leads to early wound-associated reactive oxygen species (ROS) production that mediate tissue regeneration. To identify mechanisms that function downstream of redox signals that modulate regeneration, a vimentin reporter of mesenchymal cells was generated by driving GFP from the vimentin promoter in zebrafish. Early redox signaling mediated vimentin reporter activity at the wound margin. Moreover, both ROS and vimentin were necessary for collagen production and reorganization into projections at the leading edge of the wound. Second harmonic generation time-lapse imaging revealed that the collagen projections were associated with dynamic epithelial extensions at the wound edge during wound repair. Perturbing collagen organization by burn wound disrupted epithelial projections and subsequent wound healing. Taken together our findings suggest that ROS and vimentin integrate early wound signals to orchestrate the formation of collagen-based projections that guide regenerative growth during efficient wound repair.

Article and author information

Author details

  1. Danny LeBert

    Department of Pediatrics, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Jayne M Squirrell

    Laboratory for Optical and Computational Instrumentation, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Chrissy Freisinger

    Department of Pediatrics, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Julie Rindy

    Department of Pediatrics, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Netta Golenberg

    Department of Pediatrics, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Grace Frecentes

    Laboratory for Optical and Computational Instrumentation, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Angela Gibson

    Department of Surgery, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Kevin W Eliceiri

    Laboratory for Optical and Computational Instrumentation, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Anna Huttenlocher

    Department of Pediatrics, University of Wisconsin-Madison, Madison, United States
    For correspondence
    huttenlocher@wisc.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7940-6254

Funding

National Institute of General Medical Sciences (GM1 18027 01)

  • Anna Huttenlocher

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#08-133) of the University of Wisconsin.

Reviewing Editor

  1. Fiona M Watt, King's College London, United Kingdom

Publication history

  1. Received: July 25, 2017
  2. Accepted: January 15, 2018
  3. Accepted Manuscript published: January 16, 2018 (version 1)
  4. Version of Record published: January 30, 2018 (version 2)

Copyright

© 2018, LeBert et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Danny LeBert
  2. Jayne M Squirrell
  3. Chrissy Freisinger
  4. Julie Rindy
  5. Netta Golenberg
  6. Grace Frecentes
  7. Angela Gibson
  8. Kevin W Eliceiri
  9. Anna Huttenlocher
(2018)
Damage-induced reactive oxygen species regulate vimentin and dynamic collagen-based projections to mediate wound repair
eLife 7:e30703.
https://doi.org/10.7554/eLife.30703

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