Fidgetin-Like 2: A Microtubule-Based Regulator of Wound Healing

Rabab A. Charafeddine, Joy Makdisi, David Schairer, Brian P. O'Rourke, Juan D. Diaz-Valencia, Jason Chouake, Allison Kutner, Aimee Krausz, Brandon Adler, Parimala Nacharaju, Hongying Liang, Suranjana Mukherjee, Joel M. Friedman, Adam Friedman, Joshua D. Nosanchuk, David J. Sharp

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Wound healing is a complex process driven largely by the migration of a variety of distinct cell types from the wound margin into the wound zone. In this study, we identify the previously uncharacterized microtubule-severing enzyme, Fidgetin-like 2 (FL2), as a fundamental regulator of cell migration that can be targeted in vivo using nanoparticle-encapsulated small interfering RNA (siRNA) to promote wound closure and regeneration. In vitro, depletion of FL2 from mammalian tissue culture cells results in a more than twofold increase in the rate of cell movement, in part due to a significant increase in directional motility. Immunofluorescence analyses indicate that FL2 normally localizes to the cell edge, importantly to the leading edge of polarized cells, where it regulates the organization and dynamics of the microtubule cytoskeleton. To clinically translate these findings, we utilized a nanoparticle-based siRNA delivery platform to locally deplete FL2 in both murine full-thickness excisional and burn wounds. Topical application of FL2 siRNA nanoparticles to either wound type results in a significant enhancement in the rate and quality of wound closure both clinically and histologically relative to controls. Taken together, these results identify FL2 as a promising therapeutic target to promote the regeneration and repair of cutaneous wounds.

Original languageEnglish (US)
Pages (from-to)2309-2318
Number of pages10
JournalJournal of Investigative Dermatology
Volume135
Issue number9
DOIs
StatePublished - Sep 18 2015

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Fingerprint Dive into the research topics of 'Fidgetin-Like 2: A Microtubule-Based Regulator of Wound Healing'. Together they form a unique fingerprint.

Cite this