Regenerative effects of basic fibroblast growth factor on extracellular matrix production in aged rat vocal folds.
OBJECTIVE
We investigated acute changes in extracellular matrix (ECM) gene expression and histologic changes in the deposition of collagen and hyaluronan (hyaluronic acid; HA) after basic fibroblast growth factor (bFGF) treatment of the aged rat vocal fold.


METHODS
For the polymerase chain reaction (PCR) experiments, we divided ten 18-month-old Sprague-Dawley rats into two groups that received serial injections of sham (saline solution) or bFGF (2 ng/microL) and euthanized them 2 weeks after the initial injection to investigate acute changes in ECM gene expression. We treated a separate group of 5 animals unilaterally and sacrificed them 4 weeks after the initial injection to investigate histologic changes in the deposition of collagen and HA.


RESULTS
Real-time PCR revealed significantly up-regulated HA synthase (HAS)-2, HAS-3, matrix metalloproteinase (MMP)-2, and procollagen type I gene expression in the bFGF treatment group as compared to the sham treatment group. Histologic staining revealed significantly increased deposition of HA in the bFGF-treated vocal fold as compared to the sham-treated vocal fold. No differences in ECM collagen levels were observed between treatment sides.


CONCLUSIONS
Basic fibroblast growth factor induced the up-regulation of HAS-2, HAS-3, MMP-2, and procollagen type I. Histologically, aged vocal folds treated with bFGF revealed increased deposition of HA as 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 / Q000502:physiology*; D000818:Animals; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects* / Q000473:pathology / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D000076002:Hyaluronan Synthases; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D011347:Procollagen / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000187:drug effects*; D014827:Vocal Cords / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D024042:Collagen Type I; D011347:Procollagen; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D014453:Glucuronosyltransferase; C491097:Has2 protein, rat; C491355:Has3 protein, rat; D000076002:Hyaluronan Synthases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9