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 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.
Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Sabrina
S
Schmitt
Kai
K
Safferling
Kathi
K
Westphal
Manuel
M
Hrabowski
Ute
U
Müller
Peter
P
Angel
Lars
L
Wiechert
Volker
V
Ehemann
Benedikt
B
Müller
Stefan
S
Holland-Cunz
Damian
D
Stichel
Nathalie
N
Harder
Karl
K
Rohr
Günter
G
Germann
Franziska
F
Matthäus
Peter
P
Schirmacher
Niels
N
Grabe
Kai
K
Breuhahn
D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects*; D019394:Ki-67 Antigen / Q000378:metabolism; D050777:Stathmin / Q000494:pharmacology*
D019394:Ki-67 Antigen; D050777:Stathmin