Effect of Hepatocyte Growth Factor on Gene Expression of Extracellular Matrix during Wound Healing of the Injured Rat Vocal Fold

Abstract

Objectives:

We performed a prospective, sham-controlled animal study to investigate the effects of hepatocyte growth factor (HGF) manipulation of the extracellular matrix on vocal fold gene expression during acute injury.

Methods:

Bilateral vocal fold wounds were created in 40 rats. The rats were randomly assigned to 1 of 2 groups (sham treatment or HGF treatment) and received treatment of the injured area at the time of wounding and on alternate post-treatment days. The injured vocal fold specimens were harvested on post-treatment days 1, 3, 7, and 14. We used real-time reverse transcription polymerase chain reaction to quantify messenger RNA expression of transforming growth factor (TGF)–β1, procollagen types I and III, hyaluronan synthase (HAS)–1, HAS–2, and HAS-3.

Results:

A multivariate analysis of variance revealed a significant interaction between treatment group and post-treatment day for TGF-β1, procollagen type I, procollagen type III, and HAS-2. Post hoc testing revealed significantly lower expression of procollagen type III and significantly higher expression of HAS-2 on post-treatment day 14 in the HGF treatment group than in the sham treatment group.

Conclusions:

Results provide evidence of HGF treatment effects on procollagen type III and HAS-2 gene expression pathways.

Keywords

extracellular matrix hepatocyte growth factor hyaluronan synthase procollagen transforming growth factor–β1 vocal fold wound healing

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References

Ford

Bless

. Selected problems treated by vocal fold injection of collagen. Am J Otolaryngol 1993;14:257–61.

Ford

Bless

. Collagen injection in the scarred vocal fold. J Voice 1987;1:116–8.

Staskowski

Ford

Inagi

. The histologic fate of autologous collagen injected into the canine vocal fold. Otolaryngol Head Neck Surg 1998;118:187–90.

Kriesel

Thibeault

Chan

. Treatment of vocal fold scarring: Rheological and histological measures of homologous collagen matrix. Ann Otol Rhinol Laryngol 2002;11:884–9.

Brandenburg

Kirkham

Koschkee

. Vocal cord augmentation with autogenous fat. Laryngoscope 1992;102:495–500.

Matsumoto

Nakamura

. Hepatocyte growth factor (HGF) as a tissue organizer for organogenesis and regeneration. Biochem Biophys Res Commun 1997;239:639–44.

Hirano

Bless

Rousseau

. Prevention of vocal fold scarring by topical injection of hepatocyte growth factor in a rabbit model. Laryngoscope 2004;114:548–56.

Hirano

Bless

Nagai

. Growth factor therapy for vocal fold scarring in a canine model. Ann Otol Rhinol Laryngol 2004;113:777–85.

Ohno

Hirano

Kanemaru

. Drug delivery system of hepatocyte growth factor for the treatment of vocal fold scarring in a canine model. Ann Otol Rhinol Laryngol 2007;116:762–9.

10.

Tateya

Sohn

Bless

. Histologic characterization of rat vocal fold scarring. Ann Otol Rhinol Laryngol 2005;114:183–91.

11.

Lim

Tateya

Munoz-Del-Rio

Bless

. Immediate inflammatory response and scar formation in wounded vocal folds. Ann Otol Rhinol Laryngol 2006;115:921–9.

12.

Song

Ergul

. Type-2 diabetes–induced changes in vascular extracellular matrix gene expression: Relation to vessel size. Cardiovasc Diabetol 2006;17:3.

13.

Tashiro

Hiraoka

Ikeda

. Effect of GDF-5 on ligament healing. J Orthop Res 2006;24:71–9.

14.

Oishi

Kato

Noguchi

. Dietary protein as a potent regulator of the hyaluronan synthase gene in rat skin. Biosci Biotechnol Biochem 2003;67:736–42.

15.

Fujisaki

Tanabe

Suzuki

. The effect of IL-1alpha on the expression of matrix metalloproteinases, plasminogen activators, and their inhibitors in osteoblastic ROS 17/2.8 cells. Life Sci 2006;78:1975–82.

16.

Colwell

Longaker

Lorenz

. Fetal wound healing. Front Biosci 2003;8:s1240–s1248.

17.

Ferguson

O'Kane

. Scar-free healing: From embryonic mechanisms to adult therapeutic intervention. Philos Trans R Soc Lond B Biol Sci 2004;359:839–50.

18.

Verrecchia

Mauviel

. Control of connective tissue gene expression by TGF beta: Role of Smad proteins in fibrosis. Curr Rheumatol Rep 2002;4:143–9.

19.

Roberts

Sporn

. Transforming growth factor–β. In: Clark

RAF

, ed. The molecular and cellular biology of wound repair. Vol 23. New York, NY: Plenum Press, 1996:275–308.

20.

Shah

Foreman

Ferguson

. Neutralising antibody to TGF-beta 1,2 reduces cutaneous scarring in adult rodents. J Cell Sci 1994;107:1137–57.

21.

Liu

. Hepatocyte growth factor and the kidney. Curr Opin Nephrol Hypertens 2002;11:23–30.

22.

Matsumoto

Nakamura

. Hepatocyte growth factor: Renotropic role and potential therapeutics for renal diseases. Kidney Int 2001;59:2023–38.

23.

Liu

Rajur

Tolbert

Dworkin

. Endogenous hepatocyte growth factor ameliorates chronic renal injury by activating matrix degradation pathways. Kidney Int 2000;58:2028–43.

24.

Mizuno

Nakamura

T.M

. Suppressions of chronic glomerular injuries and TGF-β1 production by HGF in attenuation of murine diabetic nephropathy. Am J Physiol Renal Physiol 2004;286:F134–F143.

25.

Thibeault

Gray

Bless

Chan

Ford

. Histologic and rheologic characterization of vocal fold scarring. J Voice 2002;16:96–104.

26.

Rousseau

Hirano

Scheidt

. Characterization of vocal fold scarring in a canine model. Laryngoscope 2003;113:620–7.

27.

Thibeault

Rousseau

Welham

Hirano

Bless

. Hyaluronan levels in acute vocal fold scar. Laryngoscope 2004;114:760–4.

28.

Rousseau

Sohn

Montequin

Tateya

Bless

. Functional outcomes of reduced hyaluronan in acute vocal fold scar. Ann Otol Rhinol Laryngol 2004;113:767–76.

29.

Weigel

Fuller

LeBoeuf

. A model for the role of hyaluronic acid and fibrin in the early events during the inflammatory response and wound healing. J Theor Biol 1986;119:219–34.

30.

Hirano

Bless

Heisey

Ford

. Roles of hepatocyte growth factor and transforming growth factor beta1 in production of extracellular matrix by canine vocal fold fibroblasts. Laryngoscope 2003;113:144–8.