title: Optimal concentration of hepatocyte growth factor for treatment of the aged rat vocal fold.
abstract: OBJECTIVE
  Hepatocyte growth factor (HGF) demonstrates beneficial properties in the treatment of aged vocal folds. However, the optimal concentration of HGF remains unknown. The purpose of the present study was to investigate the effects of HGF concentration on treatment of the aged rat vocal fold.
  
  
  METHODS
  Prospective animal study.
  
  
  METHODS
  Seventy-five rats were studied. The rats were divided into five groups and received serial injections of HGF in 10 μL of phosphate-buffered saline (PBS) at the following concentrations: 10 ng/10 μL, 50 ng/10 μL, 100 ng/10 μL, 200 ng/10 μL, or control (PBS only). Alcian blue staining was performed to investigate hyaluronan (HA), and immunohistochemistry was performed to investigate collagen type I and III. Gene expression of hyaluronic acid synthase (HAS)-1, -2, matrix metalloproteinases (MMP)-2, -9, and procollagen I and III were also investigated using real-time polymerase chain reaction (RT-PCR).
  
  
  RESULTS
  Histologic analyses revealed increased HA and decreased collagen type I in rats receiving injections of HGF at 100 ng/10 μL. Results were supported by RT-PCR revealing upregulated expression of HAS-2, decreased expression of procollagen I, and a significant increase of MMP-9 mRNA in rats receiving HGF at 100 ng/10 μL.
  
  
  CONCLUSIONS
  We report the first in vivo concentration study of HGF for treatment of the aged vocal fold. Results revealed desirable biochemical effects of HGF at 100 ng/10 μL. These data will be used to provide immediate direction to programmatic efforts aimed at examining future applications of HGF for treatment of the aged vocal fold.
authors.affiliation: Department of Otolaryngology, Vanderbilt University, Bill Wilkerson Center for Otolaryngology and Communication Sciences, Nashville, Tennessee 37232-4480, USA.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Suehiro
authors.forename: Harry
authors.initials: H
authors.lastname: Wright
authors.forename: Bernard
authors.initials: B
authors.lastname: Rousseau
mesh_terms: D000375:Aging; D000818:Animals; D003094:Collagen / Q000378:metabolism; D015870:Gene Expression; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage*; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000378:metabolism; D007150:Immunohistochemistry; D007267:Injections; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D011347:Procollagen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014827:Vocal Cords / Q000187:drug effects* / Q000378:metabolism; D014833:Voice Quality
chemical_list: D011347:Procollagen; D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor; D006820:Hyaluronic Acid; D003094:Collagen; D014453:Glucuronosyltransferase; C523794:HAS1 protein, human; D000076002:Hyaluronan Synthases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9