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Journal of Cell Science 115, 2189-2198 (2002)
© 2002 The Company of Biologists Limited

Research Article

Resistance of keratinocytes to TGFß-mediated growth restriction and apoptosis induction accelerates re-epithelialization in skin wounds

Christiane Amendt1, Amrit Mann1, Peter Schirmacher2 and Manfred Blessing1,*

1 I. Medical Department, Section Pathophysiology, Johannes Gutenberg-University, D-55131 Mainz, Germany
2 Institute of Pathology, University of Cologne, D-50931 Cologne, Germany

* Author for correspondence (e-mail: blessing{at}mail.uni-mainz.de )

Accepted 7 February 2002

The pleiotropic growth factor TGFß plays an important role in regulating responses to skin injury. TGFß targets many different cell types and is involved in all aspects of wound healing entailing inflammation, re-epithelialization, matrix formation and remodeling. To elucidate the role of TGFß signal transduction in keratinocytes during cutaneous wound healing, we have used transgenic mice expressing a dominant negative type II TGFß receptor exclusively in keratinocytes. We could demonstrate that this loss of TGFß signaling in keratinocytes led to an accelerated re-epithelialization of full thickness excisional wounds accompanied by an increased proliferation in keratinocytes at the wound edge. Furthermore, we show that impaired TGFß signaling in keratinocytes reduces apoptosis in re-epithelialized wounds of transgenic animals.

A cDNA array identified the transcription factor early growth response factor 1 (Egr1) as a target gene for TGFß in late phases of the wound healing process. As a member of the immediate-early gene family, Egr1 is upregulated shortly after injury and induces the expression of growth factor genes. We could demonstrate that Egr1 expression is also upregulated in skin wounds which have already undergone re-epithelialization. In conclusion, we attribute the enhanced re-epithelialization in our transgenics to the resistance of keratinocytes to TGFß-mediated growth restriction and apoptosis induction. We also propose a new role for TGFß induced Egr1 in late phase wound repair.

Key words: TGFß, Egr1, Wound healing, Re-epithelialization, Apoptosis, Mouse




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