¹Pharmazentrum frankfurt/ZAFES, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany

Correspondence: Dr Stefan Frank, Pharmazentrum frankfurt/ZAFES, Institut für Allgemeine Pharmakologie und Toxikologie, Klinikum der JW Goethe-Universität Frankfurt, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main/M., Germany. E-mail: S.Frank@em.uni-frankfurt.de

Received 25 April 2005; Revised 7 October 2005; Accepted 11 October 2005; Published online 29 December 2005.

Abstract

In this study, we determined regulation and function of the suppressor of cytokine signaling (SOCS)-3 in acute and impaired murine skin repair. Upon skin injury, SOCS-3 was induced and expressed during the inflammatory phase of repair. SOCS-3 protein expression was localized in a subset of non-proliferating keratinocytes within the developing wound margin epithelia. Growth factors (EGF, transforming growth factor-), nitric oxide (NO), and pro-inflammatory cytokines were inducers of SOCS-3 mRNA and protein expression in cultured human (HaCaT) and primary murine keratinocytes. Stable overexpression of SOCS-3 in HaCaT keratinocytes interfered with cytokine-induced signal transducers and activators of transcription-3 phosphorylation and inhibited serum-stimulated proliferation of the cells. Moreover, overexpression of SOCS-3 led to final differentiation of keratinocytes, which was comparable to the Ca²⁺-induced differentiation process in the cells. Finally, we determined SOCS-3 expression in two models of impaired skin repair: NO-deficient and diabetic wound healing. In line with observations from normal repair and SOCS-3 overexpression experiments, reduced keratinocyte proliferation within atrophied neo-epithelia in both models of impaired healing was associated with a marked increase in SOCS-3-expressing wound keratinocytes. In summary, this study suggests a potential novel function of SOCS-3 in regulating keratinocyte proliferation and differentiation in vitro and during skin repair in vivo.