Stathmin regulates keratinocyte proliferation and migration during cutaneous regeneration

Cutaneous regeneration utilizes paracrine feedback mechanisms to fine-tune the regulation of epidermal keratinocyte proliferation and migration. However, it is unknown how fibroblast-derived hepatocyte growth factor (HGF) affects these mutually exclusive processes in distinct cell populations. We he...

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Hauptverfasser: Schmitt, Sabrina (VerfasserIn) , Safferling, Kai (VerfasserIn) , Westphal, Kathi (VerfasserIn) , Hrabowski, Manuel (VerfasserIn) , Müller, Ute (VerfasserIn) , Angel, Peter (VerfasserIn) , Wiechert, Lars (VerfasserIn) , Ehemann, Volker (VerfasserIn) , Müller, Benedikt (VerfasserIn) , Holland-Cunz, Stefan (VerfasserIn) , Stichel, Damian (VerfasserIn) , Harder, Nathalie (VerfasserIn) , Rohr, Karl (VerfasserIn) , Germann, Günter (VerfasserIn) , Matthäus, Franziska (VerfasserIn) , Schirmacher, Peter (VerfasserIn) , Grabe, Niels (VerfasserIn) , Breuhahn, Kai (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: September 16, 2013
In: PLOS ONE
Year: 2013, Jahrgang: 8, Heft: 9, Pages: 1-15
ISSN:1932-6203
DOI:10.1371/journal.pone.0075075
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1371/journal.pone.0075075
Verlag, lizenzpflichtig, Volltext: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0075075
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Verfasserangaben:Sabrina Schmitt, Kai Safferling, Kathi Westphal, Manuel Hrabowski, Ute Müller, Peter Angel, Lars Wiechert, Volker Ehemann, Benedikt Müller, Stefan Holland-Cunz, Damian Stichel, Nathalie Harder, Karl Rohr, Günter Germann, Franziska Matthäus, Peter Schirmacher, Niels Grabe, Kai Breuhahn

MARC

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520 |a Cutaneous regeneration utilizes paracrine feedback mechanisms to fine-tune the regulation of epidermal keratinocyte proliferation and migration. However, it is unknown how fibroblast-derived hepatocyte growth factor (HGF) affects these mutually exclusive processes in distinct cell populations. We here show that HGF stimulates the expression and phosphorylation of the microtubule-destabilizing factor stathmin in primary human keratinocytes. Quantitative single cell- and cell population-based analyses revealed that basal stathmin levels are important for the migratory ability of keratinocytes in vitro; however, its expression is moderately induced in the migration tongue of mouse skin or organotypic multi-layered keratinocyte 3D cultures after full-thickness wounding. In contrast, clearly elevated stathmin expression is detectable in hyperproliferative epidermal areas. In vitro, stathmin silencing significantly reduced keratinocyte proliferation. Automated quantitative and time-resolved analyses in organotypic cocultures demonstrated a high correlation between Stathmin/phospho-Stathmin and Ki67 positivity in epidermal regions with proliferative activity. Thus, activation of stathmin may stimulate keratinocyte proliferation, while basal stathmin levels are sufficient for keratinocyte migration during cutaneous regeneration. 
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650 4 |a Growth factors 
650 4 |a Keratinocytes 
650 4 |a Mitosis 
650 4 |a Phosphorylation 
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