- 作者：Elizabeth Kiwanuka ; Florian Hackl ; Edward J. Caterson ; Daniel Nowinski ; Johan P.E. Junker ; Bengt Gerdin ; Elof Eriksson
- 关键词：Wound healing ; Re-epithelialization ; CCN2 ; Keratinocyte ; Cell migration
- 刊名：Journal of Surgical Research
- 出版年：December, 2013
- 年：2013
- 卷：185
- 期：2
- 页码：e109-e119
- 全文大小：2567 K
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聽vivo at the leading keratinocyte edge during re-epithelialization of full-thickness porcine wounds. In聽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聽vivo. The biologic importance of this was supported in聽vitro, because CCN2 regulated human keratinocyte migration through activation of the Ras-mitogen-activated protein kinase kinase-ERK signal transduction pathway.