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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Main Authors: Schmitt, Sabrina (Author) , Safferling, Kai (Author) , Westphal, Kathi (Author) , Hrabowski, Manuel (Author) , Müller, Ute (Author) , Angel, Peter (Author) , Wiechert, Lars (Author) , Ehemann, Volker (Author) , Müller, Benedikt (Author) , Holland-Cunz, Stefan (Author) , Stichel, Damian (Author) , Harder, Nathalie (Author) , Rohr, Karl (Author) , Germann, Günter (Author) , Matthäus, Franziska (Author) , Schirmacher, Peter (Author) , Grabe, Niels (Author) , Breuhahn, Kai (Author)
Format: Article (Journal)
Language:English
Published: September 16, 2013
In: PLOS ONE
Year: 2013, Volume: 8, Issue: 9, Pages: 1-15
ISSN:1932-6203
DOI:10.1371/journal.pone.0075075
Online Access: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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Author Notes: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
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Summary: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.
Item Description:Gesehen am 08.07.2021
Physical Description:Online Resource
ISSN:1932-6203
DOI:10.1371/journal.pone.0075075