Journal of investigative dermatology, 2015-09, Vol.135 (9), p.2309-2318
2015
Details
- Autor(en) / Beteiligte
- Titel
- Fidgetin-Like 2: A Microtubule-Based Regulator of Wound Healing
- Ist Teil von
- Journal of investigative dermatology, 2015-09, Vol.135 (9), p.2309-2318
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2015
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0022-202XeISSN: 1523-1747DOI: 10.1038/jid.2015.94Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4537388
- Format
- –
- Schlagworte
- Adenosine Triphosphatases - metabolism, Animals, ATPases Associated with Diverse Cellular Activities, Biopsy, Needle, Blotting, Western, Cell Movement, Cells, Cultured, Disease Models, Animal, Immunohistochemistry, Mice, Microtubule-Associated Proteins, Microtubules - drug effects, Microtubules - metabolism, Nanoparticles, Nuclear Proteins - metabolism, Random Allocation, Real-Time Polymerase Chain Reaction - methods, RNA, Small Interfering - pharmacology, Wound Healing - physiology, Wounds and Injuries - drug therapy, Wounds and Injuries - metabolism, Wounds and Injuries - pathology