Beta1 Integrin-Mediated Adhesion Signalling Is Essential for Epidermal Progenitor Cell Expansion

PLoS One. 2009;4(5):e5488. doi: 10.1371/journal.pone.0005488. Epub 2009 May 8.

Abstract

Background: There is a major discrepancy between the in vitro and in vivo results regarding the role of beta1 integrins in the maintenance of epidermal stem/progenitor cells. Studies of mice with skin-specific ablation of beta1 integrins suggested that epidermis can form and be maintained in their absence, while in vitro data have shown a fundamental role for these adhesion receptors in stem/progenitor cell expansion and differentiation.

Methodology/principal findings: To elucidate this discrepancy we generated hypomorphic mice expressing reduced beta1 integrin levels on keratinocytes that developed similar, but less severe defects than mice with beta1-deficient keratinocytes. Surprisingly we found that upon aging these abnormalities attenuated due to a rapid expansion of cells, which escaped or compensated for the down-regulation of beta1 integrin expression. A similar phenomenon was observed in aged mice with a complete, skin-specific ablation of the beta1 integrin gene, where cells that escaped Cre-mediated recombination repopulated the mutant skin in a very short time period. The expansion of beta1 integrin expressing keratinocytes was even further accelerated in situations of increased keratinocyte proliferation such as wound healing.

Conclusions/significance: These data demonstrate that expression of beta1 integrins is critically important for the expansion of epidermal progenitor cells to maintain epidermal homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism
  • Alleles
  • Animals
  • Cell Adhesion
  • Cell Count
  • Cell Proliferation
  • Codon, Nonsense / genetics
  • Crosses, Genetic
  • Epidermal Cells*
  • Epidermis / metabolism*
  • Female
  • Gene Deletion
  • Genotype
  • Heterozygote
  • Integrases / metabolism
  • Integrin beta1 / metabolism*
  • Keratin-5 / metabolism
  • Keratinocytes / cytology
  • Keratinocytes / metabolism
  • Male
  • Mice
  • Phenotype
  • Recombination, Genetic / genetics
  • Signal Transduction*
  • Skin / metabolism
  • Skin / pathology
  • Stem Cells / cytology*
  • Stem Cells / metabolism*

Substances

  • Codon, Nonsense
  • Integrin beta1
  • Keratin-5
  • Cre recombinase
  • Integrases