Regeneration of aged rat vocal folds using hepatocyte growth factor therapy.
OBJECTIVE
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.


METHODS
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/microL) 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.
Ohno
Tsunehisa
T
Department of Otolaryngology, Vanderbilt University Bill Wilkerson Center for Otolaryngology and Communication Sciences, Nashville, Tennessee 37232-4480, USA.
Yoo
Mi Jin
MJ
Swanson
Erik R
ER
Hirano
Shigeru
S
Ossoff
Robert H
RH
Rousseau
Bernard
B
D000375:Aging / Q000378:metabolism*; D000818:Animals; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000737:chemistry; D015870:Gene Expression; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006820:Hyaluronic Acid / Q000235:genetics / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D011446:Prospective Studies; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000187:drug effects* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D014827:Vocal Cords / Q000293:injuries*; D014945:Wound Healing / Q000187:drug effects* / Q000235:genetics
D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor; D006820:Hyaluronic Acid; D003094:Collagen; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9