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Article
Epithelial Cells Are Active Participants in Vocal Fold Wound Healing: An In Vivo Animal Model of Injury
PLoS ONE
  • Ciara Leydon, Sacred Heart University
  • Mitsuyoshi Imaizumi
  • Rebecca S. Bartlett
  • Sarah F. Wang
  • Susan L. Thibeault
Document Type
Peer-Reviewed Article
Publication Date
12-16-2014
Abstract

Vocal fold epithelial cells likely play an important, yet currently poorly defined, role in healing following injury, irritation and inflammation. In the present study, we sought to identify a possible role for growth factors, epidermal growth factor (EGF) and transforming growth factor-beta 1 (TGFβ1), in epithelial regeneration during wound healing as a necessary first step for uncovering potential signaling mechanisms of vocal fold wound repair and remodeling. Using a rat model, we created unilateral vocal fold injuries and examined the timeline for epithelial healing and regeneration during early and late stages of wound healing using immunohistochemistry (IHC). We observed time-dependent secretion of the proliferation marker, ki67, growth factors EGF and TGFβ1, as well as activation of the EGF receptor (EGFR), in regenerating epithelium during the acute phase of injury. Ki67, growth factor, and EGFR expression peaked at day 3 post-injury. Presence of cytoplasmic and intercellular EGF and TGFβ1 staining occurred up to 5 days post-injury, consistent with a role for epithelial cells in synthesizing and secreting these growth factors. To confirm that epithelial cells contributed to the cytokine secretion, we examined epithelial cell growth factor secretion in vitro using polymerase chain reaction (PCR). Cultured pig vocal fold epithelial cells expressed both EGF and TGFβ1. Our in vivo and in vitro findings indicate that epithelial cells are active participants in the wound healing process. The exact mechanisms underlying their roles in autocrine and paracrine signaling guiding wound healing await study in a controlled, in vitro environment.

Comments

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

This work was supported by the National Institutes of Health National Institute of Deafness and Other Communication Disorders DC R03 DC011355 (CL) and R01 DC012773 (ST). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

DOI
10.1371/journal.pone. 0115389
PMID
25514022
Citation Information

Leydon C, Imaizumi M, Bartlett RS, Wang SF, Thibeault SL (2014) Epithelial Cells Are Active Participants in Vocal Fold Wound Healing: An In Vivo Animal Model of Injury. PLoS ONE 9(12): e115389. doi:10.1371/journal.pone. 0115389