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...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| 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 |
| 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 |
| 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 |