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Overexpression of mIGF-1 in keratinocytes improves wound healing and accelerates hair follicle formation and cycling in mice.
Semenova E, Koegel H, Hasse S, Klatte J, Slonimsky E, Bilbao D, Paus RR, Werner S, Rosenthal N
Am J Pathol. 2008;173( 5):1295-310.
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Abstract
Insulin-like growth factor 1 (IGF-1) is an important regulator of growth, survival, and differentiation in many tissues. It is produced in several isoforms that differ in their N-terminal signal peptide and C-terminal extension peptide. The locally acting isoform of IGF-1 (mIGF-1) was previously shown to enhance the regeneration of both muscle and heart. In this study, we tested the therapeutic potential of mIGF-1 in the skin by generating a transgenic mouse model in which mIGF-1 expression is driven by the keratin 14 promoter. IGF-1 levels were unchanged in the sera of hemizygous K14/mIGF-1 transgenic animals whose growth was unaffected. A skin analysis of young animals revealed normal architecture and thickness as well as proper expression of differentiation and proliferation markers. No malignant tumors were formed. Normal homeostasis of the putative stem cell compartment was also maintained. Healing of full-thickness excisional wounds was accelerated because of increased proliferation and migration of keratinocytes, whereas inflammation, granulation tissue formation, and scarring were not obviously affected. In addition, mIGF-1 promoted late hair follicle morphogenesis and cycling. To our knowledge, this is the first work to characterize the simultaneous, stimulatory effect of IGF-1 delivery to keratinocytes on two types of regeneration processes within a single mouse model. Our analysis supports the use of mIGF-1 for skin and hair regeneration and describes a potential cell type-restricted action.
Keyword(s)
Animals; Cell Cycle; Cell Differentiation; Cell Movement; Cell Proliferation; Flow Cytometry; Gene Expression Regulation; Homeostasis; Mice; Mice, Transgenic; Morphogenesis; Phenotype; Rats; Transgenes; Wound Healing; cytology: Hair Follicle; cytology: Keratinocytes; cytology: Skin; cytology: Stromal Cells; genetics: Insulin-Like Growth Factor I; metabolism: Epithelium; metabolism: Keratin-14