Hepatocyte growth factor and keratinocyte growth factor regulation of epithelial and stromal corneal wound healing

Louise M. Carrington, Mike Boulton

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Purpose: To investigate the effects of hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF) on early wound healing in the corneal epithelium and stroma. Setting: Cell and Molecular Biology Unit, Department of Optometry and Vision Sciences, Cardiff University, and the Cardiff Institute of Tissue Engineering and Repair, Cardiff, United Kingdom. Methods: Corneal keratocyte cell cultures and wounded corneal organ cultures (both maintained in serum-free conditions) were treated with 0.1 to 100 ng/mL of HGF or KGF for up to 5 days. Cell cultures were assessed for proliferation, migration, and differentiation into myofibroblasts. Organ cultures were used to evaluate the effect of HGF and KGF on reepithelialization following a wound, epithelial morphology and stratification, keratocyte numbers directly beneath the wounded area, and differentiation into myofibroblasts. Results: The 2 growth factors had opposite effects on the rate of reepithelialization, with HGF delaying and KGF accelerating epitlial coverage of the wound. Morphologic assessment showed that both growth factors affected the stratification and differentiation of the epithelium. Both factors stimulated proliferation of keratocytes in serum-free cell culture, although neither induced the appearance of myofibroblasts. This was in contrast to wounded organ cultures treated with 100 ng/mL HGF, in which large numbers of myofibroblasts were observed under the wound. Control corneas and those receiving KGF contained very few myofibroblasts. Keratocyte repopulation of the denuded area under the wound was enhanced in the presence of HGF but decreased in response to KGF. Conclusions: Hepatocyte growth factor and KGF appeared to have potent and often opposite effects on epithelial and stromal cells following a wound. Hepatocyte growth factor was more detrimental than KGF, resulting in an aberrant epithelium and mass differentiation of keratocytes into myofibroblasts. Inhibition of HGF may be an appropriate therapeutic intervention in the case of persistent epithelial defects and to prevent fibrosis following a corneal stromal wound such as can occur after refractive surgery.

Original languageEnglish (US)
Pages (from-to)412-423
Number of pages12
JournalJournal of Cataract and Refractive Surgery
Volume31
Issue number2
DOIs
StatePublished - Feb 2005
Externally publishedYes

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Fibroblast Growth Factor 7
Hepatocyte Growth Factor
Wound Healing
Myofibroblasts
Organ Culture Techniques
Wounds and Injuries
Cell Culture Techniques
Intercellular Signaling Peptides and Proteins
Corneal Keratocytes
Epithelium
Optometry
Corneal Stroma
Refractive Surgical Procedures
Corneal Epithelium
Tissue Engineering
Stromal Cells
Serum
Cornea
Cell Biology
Molecular Biology

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Hepatocyte growth factor and keratinocyte growth factor regulation of epithelial and stromal corneal wound healing. / Carrington, Louise M.; Boulton, Mike.

In: Journal of Cataract and Refractive Surgery, Vol. 31, No. 2, 02.2005, p. 412-423.

Research output: Contribution to journalArticle

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abstract = "Purpose: To investigate the effects of hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF) on early wound healing in the corneal epithelium and stroma. Setting: Cell and Molecular Biology Unit, Department of Optometry and Vision Sciences, Cardiff University, and the Cardiff Institute of Tissue Engineering and Repair, Cardiff, United Kingdom. Methods: Corneal keratocyte cell cultures and wounded corneal organ cultures (both maintained in serum-free conditions) were treated with 0.1 to 100 ng/mL of HGF or KGF for up to 5 days. Cell cultures were assessed for proliferation, migration, and differentiation into myofibroblasts. Organ cultures were used to evaluate the effect of HGF and KGF on reepithelialization following a wound, epithelial morphology and stratification, keratocyte numbers directly beneath the wounded area, and differentiation into myofibroblasts. Results: The 2 growth factors had opposite effects on the rate of reepithelialization, with HGF delaying and KGF accelerating epitlial coverage of the wound. Morphologic assessment showed that both growth factors affected the stratification and differentiation of the epithelium. Both factors stimulated proliferation of keratocytes in serum-free cell culture, although neither induced the appearance of myofibroblasts. This was in contrast to wounded organ cultures treated with 100 ng/mL HGF, in which large numbers of myofibroblasts were observed under the wound. Control corneas and those receiving KGF contained very few myofibroblasts. Keratocyte repopulation of the denuded area under the wound was enhanced in the presence of HGF but decreased in response to KGF. Conclusions: Hepatocyte growth factor and KGF appeared to have potent and often opposite effects on epithelial and stromal cells following a wound. Hepatocyte growth factor was more detrimental than KGF, resulting in an aberrant epithelium and mass differentiation of keratocytes into myofibroblasts. Inhibition of HGF may be an appropriate therapeutic intervention in the case of persistent epithelial defects and to prevent fibrosis following a corneal stromal wound such as can occur after refractive surgery.",
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