title: Differentiated epidermal cells regain the ability to regenerate a skin equivalent by increasing the level of β-catenin in the cells.
abstract: Epidermal stem cells are of major importance for skin regeneration and tissue engineering, but differentiated epidermal cells lost their proliferative capacity and are no longer able to regenerate a skin equivalent. Here, we investigated the role of β-catenin in regulating regenerative functions of differentiated epidermal cells. Lithium chloride and a highly specific glycogen synthase kinase (GSK)-3β inhibitor were applied to induce the expression of β-catenin in differentiated epidermal cells. After a 6-day induction, the large flat-shaped cells with a small nuclear-cytoplasmic ratio had changed into small round-shaped cells with a large nuclear-cytoplasmic ratio. Phenotypic assays showed a remarkably higher expression of CK19, β(1)-integrin, Oct4 and Nanog in induced cells than in the control group (p < 0.01). In addition, the results of growth and functional investigations demonstrated that the induced epidermal cells exhibited a high colony-forming ability, a long-term proliferative potential and the ability to regenerate a skin equivalent, which were regarded as the most important features of epidermal stem cells. These results suggest that the activation of β-catenin favors the reversion or dedifferentiation of differentiated epidermal cells to an immature or a less differentiated state. This study may also offer a new approach to yield enough epidermal stem cells for skin regeneration and tissue engineering.
authors.affiliation: Laser and Aesthetic Surgery Center, Dermatology Institute, General Hospital of Beijing Military Command, Beijing, China.
authors.forename: Zhili
authors.initials: Z
authors.lastname: Zhao
authors.forename: Cuiping
authors.initials: C
authors.lastname: Zhang
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Fu
authors.forename: Rongya
authors.initials: R
authors.lastname: Yang
authors.forename: Chen
authors.initials: C
authors.lastname: Peng
authors.forename: Tingmin
authors.initials: T
authors.lastname: Gu
authors.forename: Zhifu
authors.initials: Z
authors.lastname: Sui
authors.forename: Congmin
authors.initials: C
authors.lastname: Wang
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D048708:Cell Growth Processes / Q000187:drug effects / Q000502:physiology; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007150:Immunohistochemistry; D018021:Lithium Chloride / Q000494:pharmacology; D012038:Regeneration / Q000187:drug effects / Q000502:physiology*; D012879:Skin Physiological Phenomena; D051176:beta Catenin / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D051176:beta Catenin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride