Abstract
Background
CCN2 (previously known as connective tissue growth factor) is a multifunctional matricellular
protein that has numerous effects on cell life and cell interactions with the connective
tissue. Although the importance of CCN2 for the fibrotic process in wound healing
has been well studied, the involvement of CCN2 in keratinocyte function has not yet
been explored. Therefore, the aim of the present study was to investigate the role
of CCN2 in the epidermis during wound healing.
Materials and methods
Immunohistochemistry was done on sections from full-thickness porcine wounds. The
effect of CCN2 on the migration of cultured human keratinocytes exposed to scratch
wounds, the effect on phosphorylation of extracellular signal-related kinases (ERK),
and the effect of adding inhibitors to the ERK/mitogen-activated protein kinase pathway
to human keratinocytes were studied.
Results
The CCN2 protein was transiently expressed in vivo at the leading keratinocyte edge during re-epithelialization of full-thickness porcine
wounds. In vitro, exogenous addition of CCN2 to human keratinocyte cultures regulated keratinocyte
migration and resulted in phosphorylation of ERK. The addition of inhibitors of ERK/mitogen-activated
protein kinase counteracted the effect of CCN2 on migration.
Conclusions
CCN2 was transiently expressed at the leading keratinocyte edge in vivo. The biologic importance of this was supported in vitro, because CCN2 regulated human keratinocyte migration through activation of the Ras-mitogen-activated
protein kinase kinase-ERK signal transduction pathway.
Keywords
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Article info
Publication history
Published online: June 10, 2013
Accepted:
May 15,
2013
Received in revised form:
May 8,
2013
Received:
January 3,
2013
Identification
Copyright
Published by Elsevier Inc.
