HGF, MAPK, and a small physiological electric field interact during corneal epithelial cell migration

Vikki Anne McBain, John Vincent Forrester, Colin Darnley McCaig

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

PURPOSE. To investigate the effects of hepatocyte growth factor (HGF) and a small applied electric field (EF) on corneal epithelial cell (CEC) migration.

METHODS. Primary cultures of bovine CECs were exposed to an EF (25-250 mV/mm) in the presence or absence of HGF (100 ng/mL). The rate and directionality of CEC migration were quantified. The expression of HGF receptors (HGFRs), p42/44 mitogen activated protein kinase (MAPK) and the time-course of activation of p42/44 MAPK were investigated by confocal microscopy and Western blot analysis.

RESULTS. CECs migrated significantly faster in the presence of an EF, HGF, or HGF and an EF combined. The distribution of HGFRs was intracellular and in the presence of an EF was concentrated in the cathode-facing side. This EF-induced asymmetrical accumulation of HGFRs correlated with the direction of CEC migration. The application of HGF or an EF led to the activation of the MAPK signaling pathway and in the presence of an EF, activation of MAPK was greater in the cathode-facing half of the CECs. Inhibition of the MAPK signaling pathway by PD98059 (100 muM) reduced the ability of HGF and an EF to enhance the rate of CEC migration, but did not alter EF-induced cathodal directionality.

CONCLUSIONS. These data suggest that both HGF and an EF augment the rate of CEC migration through activation of p42/44 MAPK Moreover, EF-induced redistribution of HGFRs and asymmetry of MAPK signaling, although not instrumental in directing CEC migration cathodally, may be important for the signaling and maintenance of migration.

Original languageEnglish
Pages (from-to)540-547
Number of pages7
JournalInvestigative Ophthalmology & Visual Science
Volume44
Issue number2
DOIs
Publication statusPublished - 2003

Keywords

  • HEPATOCYTE GROWTH-FACTOR
  • ACTIVATED PROTEIN-KINASE
  • FACTOR SCATTER FACTOR
  • ACTIN STRESS FIBERS
  • TYROSINE PHOSPHORYLATION
  • C-MET
  • PHOSPHATIDYLINOSITOL 3-KINASE
  • NOTOPHTHALMUS-VIRIDESCENS
  • HUMAN KERATINOCYTES
  • FACTOR RECEPTORS

Cite this

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title = "HGF, MAPK, and a small physiological electric field interact during corneal epithelial cell migration",
abstract = "PURPOSE. To investigate the effects of hepatocyte growth factor (HGF) and a small applied electric field (EF) on corneal epithelial cell (CEC) migration.METHODS. Primary cultures of bovine CECs were exposed to an EF (25-250 mV/mm) in the presence or absence of HGF (100 ng/mL). The rate and directionality of CEC migration were quantified. The expression of HGF receptors (HGFRs), p42/44 mitogen activated protein kinase (MAPK) and the time-course of activation of p42/44 MAPK were investigated by confocal microscopy and Western blot analysis.RESULTS. CECs migrated significantly faster in the presence of an EF, HGF, or HGF and an EF combined. The distribution of HGFRs was intracellular and in the presence of an EF was concentrated in the cathode-facing side. This EF-induced asymmetrical accumulation of HGFRs correlated with the direction of CEC migration. The application of HGF or an EF led to the activation of the MAPK signaling pathway and in the presence of an EF, activation of MAPK was greater in the cathode-facing half of the CECs. Inhibition of the MAPK signaling pathway by PD98059 (100 muM) reduced the ability of HGF and an EF to enhance the rate of CEC migration, but did not alter EF-induced cathodal directionality.CONCLUSIONS. These data suggest that both HGF and an EF augment the rate of CEC migration through activation of p42/44 MAPK Moreover, EF-induced redistribution of HGFRs and asymmetry of MAPK signaling, although not instrumental in directing CEC migration cathodally, may be important for the signaling and maintenance of migration.",
keywords = "HEPATOCYTE GROWTH-FACTOR, ACTIVATED PROTEIN-KINASE, FACTOR SCATTER FACTOR, ACTIN STRESS FIBERS, TYROSINE PHOSPHORYLATION, C-MET, PHOSPHATIDYLINOSITOL 3-KINASE, NOTOPHTHALMUS-VIRIDESCENS, HUMAN KERATINOCYTES, FACTOR RECEPTORS",
author = "McBain, {Vikki Anne} and Forrester, {John Vincent} and McCaig, {Colin Darnley}",
year = "2003",
doi = "10.1167/iovs.02-0570",
language = "English",
volume = "44",
pages = "540--547",
journal = "Investigative Ophthalmology & Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "2",

}

TY - JOUR

T1 - HGF, MAPK, and a small physiological electric field interact during corneal epithelial cell migration

AU - McBain, Vikki Anne

AU - Forrester, John Vincent

AU - McCaig, Colin Darnley

PY - 2003

Y1 - 2003

N2 - PURPOSE. To investigate the effects of hepatocyte growth factor (HGF) and a small applied electric field (EF) on corneal epithelial cell (CEC) migration.METHODS. Primary cultures of bovine CECs were exposed to an EF (25-250 mV/mm) in the presence or absence of HGF (100 ng/mL). The rate and directionality of CEC migration were quantified. The expression of HGF receptors (HGFRs), p42/44 mitogen activated protein kinase (MAPK) and the time-course of activation of p42/44 MAPK were investigated by confocal microscopy and Western blot analysis.RESULTS. CECs migrated significantly faster in the presence of an EF, HGF, or HGF and an EF combined. The distribution of HGFRs was intracellular and in the presence of an EF was concentrated in the cathode-facing side. This EF-induced asymmetrical accumulation of HGFRs correlated with the direction of CEC migration. The application of HGF or an EF led to the activation of the MAPK signaling pathway and in the presence of an EF, activation of MAPK was greater in the cathode-facing half of the CECs. Inhibition of the MAPK signaling pathway by PD98059 (100 muM) reduced the ability of HGF and an EF to enhance the rate of CEC migration, but did not alter EF-induced cathodal directionality.CONCLUSIONS. These data suggest that both HGF and an EF augment the rate of CEC migration through activation of p42/44 MAPK Moreover, EF-induced redistribution of HGFRs and asymmetry of MAPK signaling, although not instrumental in directing CEC migration cathodally, may be important for the signaling and maintenance of migration.

AB - PURPOSE. To investigate the effects of hepatocyte growth factor (HGF) and a small applied electric field (EF) on corneal epithelial cell (CEC) migration.METHODS. Primary cultures of bovine CECs were exposed to an EF (25-250 mV/mm) in the presence or absence of HGF (100 ng/mL). The rate and directionality of CEC migration were quantified. The expression of HGF receptors (HGFRs), p42/44 mitogen activated protein kinase (MAPK) and the time-course of activation of p42/44 MAPK were investigated by confocal microscopy and Western blot analysis.RESULTS. CECs migrated significantly faster in the presence of an EF, HGF, or HGF and an EF combined. The distribution of HGFRs was intracellular and in the presence of an EF was concentrated in the cathode-facing side. This EF-induced asymmetrical accumulation of HGFRs correlated with the direction of CEC migration. The application of HGF or an EF led to the activation of the MAPK signaling pathway and in the presence of an EF, activation of MAPK was greater in the cathode-facing half of the CECs. Inhibition of the MAPK signaling pathway by PD98059 (100 muM) reduced the ability of HGF and an EF to enhance the rate of CEC migration, but did not alter EF-induced cathodal directionality.CONCLUSIONS. These data suggest that both HGF and an EF augment the rate of CEC migration through activation of p42/44 MAPK Moreover, EF-induced redistribution of HGFRs and asymmetry of MAPK signaling, although not instrumental in directing CEC migration cathodally, may be important for the signaling and maintenance of migration.

KW - HEPATOCYTE GROWTH-FACTOR

KW - ACTIVATED PROTEIN-KINASE

KW - FACTOR SCATTER FACTOR

KW - ACTIN STRESS FIBERS

KW - TYROSINE PHOSPHORYLATION

KW - C-MET

KW - PHOSPHATIDYLINOSITOL 3-KINASE

KW - NOTOPHTHALMUS-VIRIDESCENS

KW - HUMAN KERATINOCYTES

KW - FACTOR RECEPTORS

U2 - 10.1167/iovs.02-0570

DO - 10.1167/iovs.02-0570

M3 - Article

VL - 44

SP - 540

EP - 547

JO - Investigative Ophthalmology & Visual Science

JF - Investigative Ophthalmology & Visual Science

SN - 0146-0404

IS - 2

ER -