Regulation of wound healing by granulocyte-macrophage colony-stimulating factor after vocal fold injury.
OBJECTIVES: 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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3556034?pdf=render |
| _version_ | 1818852832211632128 |
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| author | Jae-Yol Lim Byung Hyune Choi Songyi Lee Yun Ho Jang Jeong-Seok Choi Young-Mo Kim |
| author_facet | Jae-Yol Lim Byung Hyune Choi Songyi Lee Yun Ho Jang Jeong-Seok Choi Young-Mo Kim |
| author_sort | Jae-Yol Lim |
| collection | DOAJ |
| description | OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSION: The present study shows that GM-CSF offers therapeutic potential for the remodeling of VF wounds and the promotion of VF regeneration. |
| first_indexed | 2024-12-19T07:27:11Z |
| format | Article |
| id | doaj.art-bca00b33a1494c18a8f45ef9b4af3097 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T07:27:11Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-bca00b33a1494c18a8f45ef9b4af30972022-12-21T20:30:48ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0181e5425610.1371/journal.pone.0054256Regulation of wound healing by granulocyte-macrophage colony-stimulating factor after vocal fold injury.Jae-Yol LimByung Hyune ChoiSongyi LeeYun Ho JangJeong-Seok ChoiYoung-Mo KimOBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSION: The present study shows that GM-CSF offers therapeutic potential for the remodeling of VF wounds and the promotion of VF regeneration.http://europepmc.org/articles/PMC3556034?pdf=render |
| spellingShingle | Jae-Yol Lim Byung Hyune Choi Songyi Lee Yun Ho Jang Jeong-Seok Choi Young-Mo Kim Regulation of wound healing by granulocyte-macrophage colony-stimulating factor after vocal fold injury. PLoS ONE |
| title | Regulation of wound healing by granulocyte-macrophage colony-stimulating factor after vocal fold injury. |
| title_full | Regulation of wound healing by granulocyte-macrophage colony-stimulating factor after vocal fold injury. |
| title_fullStr | Regulation of wound healing by granulocyte-macrophage colony-stimulating factor after vocal fold injury. |
| title_full_unstemmed | Regulation of wound healing by granulocyte-macrophage colony-stimulating factor after vocal fold injury. |
| title_short | Regulation of wound healing by granulocyte-macrophage colony-stimulating factor after vocal fold injury. |
| title_sort | regulation of wound healing by granulocyte macrophage colony stimulating factor after vocal fold injury |
| url | http://europepmc.org/articles/PMC3556034?pdf=render |
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