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Regeneration of aged rat vocal folds using hepatocyte growth factor therapy

Authors

  • Tsunehisa Ohno MD,

    1. Department of Otolaryngology, Vanderbilt University Bill Wilkerson Center for Otolaryngology and Communication Sciences, Nashville, Tennessee, U.S.A.
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  • Mi Jin Yoo BA,

    1. Department of Otolaryngology, Vanderbilt University Bill Wilkerson Center for Otolaryngology and Communication Sciences, Nashville, Tennessee, U.S.A.
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  • Erik R. Swanson MD,

    1. Department of Otolaryngology, Vanderbilt University Bill Wilkerson Center for Otolaryngology and Communication Sciences, Nashville, Tennessee, U.S.A.
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  • Shigeru Hirano MD, PhD,

    1. Department of Otolaryngology-Head & Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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  • Robert H. Ossoff DMD, MD,

    1. Department of Otolaryngology, Vanderbilt University Bill Wilkerson Center for Otolaryngology and Communication Sciences, Nashville, Tennessee, U.S.A.
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  • Bernard Rousseau PhD

    Corresponding author
    1. Department of Otolaryngology, Vanderbilt University Bill Wilkerson Center for Otolaryngology and Communication Sciences, Nashville, Tennessee, U.S.A.
    • Vanderbilt University, Department of Otolaryngology, 1313 21st Avenue South, Room 602, Nashville, TN 37232-4480
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  • Presented at the American Laryngological Association Combined Sections Meeting, Phoenix, Arizona, U.S.A., May 28–29, 2009.

  • Recipient of the 2009 Young Faculty/Practitioner Award of the American Laryngological Association.

Abstract

Objectives/Hypothesis:

We investigated acute changes in extracellular matrix gene expression and histologic changes in the deposition of collagen and hyaluronan (HA) from hepatocyte growth factor (HGF) treatment of the aged rat vocal fold. We hypothesized that: 1) HGF induces matrix metalloproteinase gene expression, which might contribute to the downregulation of collagen; and 2) HGF induces hyaluronan synthase (HAS) gene expression, which might play a role in the upregulation of extracellular matrix HA.

Study Design:

Prospective animal study.

Methods:

Fifteen, 18-month-old, Sprague-Dawley rats were involved in this study. For gene expression analyses, 10 rats were divided into two groups and received serial injections of sham (saline) or HGF (2 ng/μL) and sacrificed 2 weeks after the initial injection to investigate acute changes in extracellular matrix gene expression. A separate group of five animals received the above treatment and were sacrificed 4 weeks after the initial injection to investigate histologic changes in the deposition of collagen and HA.

Results:

Real-time polymerase chain reaction revealed significantly upregulated matrix metalloproteinase(MMP)-2, -9, and HAS-3 messenger RNA (mRNA) expression and significantly downregulated procollagen type I mRNA expression in the HGF-treatment group, compared to the sham-treatment group. Histologic staining revealed significantly reduced collagen deposition and increased deposition of HA in the HGF-treated vocal fold, compared to the sham-treated vocal fold.

Conclusions:

HGF induced the upregulation of MMP-2, -9, and HAS-3, and downregulated the expression of procollagen type I. Histologically, aged vocal folds treated with HGF revealed decreased collagen deposition, and increased deposition of HA, compared to sham-treated vocal folds. Laryngoscope, 2009

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