Regulation of wound healing by granulocyte-macrophage colony-stimulating factor after vocal fold injury

• Published in: PloS one Vol. 8; no. 1; p. e54256
• Main Authors: Lim, Jae-Yol, Choi, Byung Hyune, Lee, Songyi, Jang, Yun Ho, Choi, Jeong-Seok, Kim, Young-Mo
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 25.01.2013; Public Library of Science (PLoS)
• Subjects: Acids; Animals; Biology; Biomechanics; c-Met protein; Cells, Cultured; Collagen; Collagen (type I); Collagen Type I - antagonists & inhibitors; Collagen Type I - genetics; Collagen Type I - metabolism; Collagen Type III - genetics; Collagen Type III - metabolism; Colonies; Colony-stimulating factor; Cytokines; Elastin; Elastin - genetics; Elastin - metabolism; Enzyme-linked immunosorbent assay; Experiments; Extracellular matrix; Extracellular Matrix - drug effects; Extracellular Matrix - genetics; Extracellular Matrix - metabolism; Fibroblasts; Fibroblasts - cytology; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibronectin; Fibronectins; Fibronectins - antagonists & inhibitors; Fibronectins - genetics; Fibronectins - metabolism; Gene expression; Gene Expression - drug effects; Granulocyte-macrophage colony-stimulating factor; Granulocyte-Macrophage Colony-Stimulating Factor - metabolism; Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology; Granulocytes; Growth factors; Health aspects; Hepatocyte Growth Factor - genetics; Hepatocyte Growth Factor - metabolism; Humans; Hyaluronic Acid - biosynthesis; Immunohistochemistry; In vitro methods and tests; In vivo methods and tests; Injections, Intralesional; Injuries; Interstitial collagenase; Macrophage colony stimulating factor; Macrophages; Matrix metalloproteinase; Medicine; mRNA; Mucosa; Otolaryngology; Polymerase chain reaction; Rabbits; Regeneration; RNA; Scars; Studies; Surgery; Synthesis; Tissue engineering; Transforming Growth Factor beta1 - genetics; Transforming Growth Factor beta1 - metabolism; Transforming growth factor-b1; Transforming growth factors; Tropoelastin; Vocal Cords - drug effects; Vocal Cords - injuries; Vocal Cords - metabolism; Wound care; Wound healing; Wound Healing - drug effects; Wound Healing - physiology; South Korea
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0054256

Vocal fold (VF) scarring remains a therapeutic challenge. Granulocyte-macrophage colony-stimulating factor (GM-CSF) facilitates epithelial wound healing, and recently, growth factor therapy has been applied to promote tissue repair. This study was undertaken to investigate the effect of GM-CSF on VF wound healing in vivo and in vitro. VF scarring was induced in New Zealand white rabbits by direct injury. Immediately thereafter, either GM-CSF or PBS was injected into the VFs of rabbits. Endoscopic, histopathological, immunohistochemical, and biomechanical evaluations of VFs were performed at 3 months post-injury. Human vocal fold fibroblasts (hVFFs) were cultured with GM-CSF. Production of type I and III collagen was examined immunocytochemically, and the synthesis of elastin and hyaluronic acids was evaluated by ELISA. The mRNA levels of genes related to ECM components and ECM production-related growth factors, such as HGF and TGF-ß1, were examined by real time RT-PCR. The GM-CSF-treated VFs showed reduced collagen deposition in comparison to the PBS-injected controls (P<0.05). Immunohistochemical staining revealed lower amounts of type I collagen and fibronectin in the GM-CSF-treated VFs (P<0.05 and P<0.01, respectively). Viscous and elastic shear moduli of VF samples were significantly lower in the GM-CSF group than in the PBS-injected group (P<0.001 and P<0.01, respectively). Mucosal waves in the GM-CSF group showed significant improvement when compared to the PBS group (P = 0.0446). GM-CSF inhibited TGF-β1-induced collagen synthesis by hVFFs (P<0.05) and the production of hyaluronic acids increased at 72 hours post-treatment (P<0.05). The expressions of HAS-2, tropoelastin, MMP-1, HGF, and c-Met mRNA were significantly increased by GM-CSF, although at different time points (P<0.05). The present study shows that GM-CSF offers therapeutic potential for the remodeling of VF wounds and the promotion of VF regeneration.