title: Somatostatin inhibits cell migration and reduces cell counts of human keratinocytes and delays epidermal wound healing in an ex vivo wound model.
abstract: The peptide hormone somatostatin (SST) and its five G protein-coupled receptors (SSTR1-5) were described to be present in the skin, but their cutaneous function(s) and skin-specific signalling mechanisms are widely unknown. By using receptor specific agonists we show here that the SSTRs expressed in keratinocytes are functionally coupled to the inhibition of adenylate cyclase. In addition, treatment with SSTR4 and SSTR5/1 specific agonists significantly influences the MAP kinase signalling pathway. As epidermal hormone receptors in general are known to regulate re-epithelialization following skin injury, we investigated the effect of SST on cell counts and migration of human keratinocytes. Our results demonstrate a significant inhibition of cell migration and reduction of cell counts by SST. We do not observe an effect on apoptosis and necrosis. Analysis of signalling pathways showed that somatostatin inhibits cell migration independent of its effect on cAMP. Migrating keratinocytes treated with SST show altered cytoskeleton dynamics with delayed lamellipodia formation. Furthermore, the activity of the small GTPase Rac1 is diminished, providing evidence for the control of the actin cytoskeleton by somatostatin receptors in keratinocytes. While activation of all receptors leads to redundant effects on cell migration, only treatment with a SSTR5/1 specific agonist resulted in decreased cell counts. In accordance with reduced cell counts and impaired migration we observe delayed re-epithelialization in an ex vivo wound healing model. Consequently, our experiments suggest SST as a negative regulator of epidermal wound healing.
authors: Department of Dermatology and Venerology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors: Matthias
authors: M
authors: Vockel
authors: Simone
authors: S
authors: Pollok
authors: Ute
authors: U
authors: Breitenbach
authors: Ina
authors: I
authors: Ridderbusch
authors: Hans-Jürgen
authors: HJ
authors: Kreienkamp
authors: Johanna M
authors: JM
authors: Brandner
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